Common Variable Immunodeficiency

On this page

Quick Reference

RxDrug of choiceImmunoglobulin replacement therapy (IVIG 400-600 mg/kg q3-4wk or SCIG 100-200 mg/kg weekly) titrated to individual trough.

AltAlternativesAntimicrobial prophylaxis (TMP-SMX DS daily or azithromycin 250 mg TIW); for non-infectious complications: prednisone ≥0.3 mg/kg/day, rituximab 150-375 mg/m², abatacept (CTLA-4 insufficiency), sirolimus (LRBA deficiency), omalizumab (CSU), PD-1 inhibitors (malignancy).

⊘AvoidLive vaccines; IgA-containing IVIG in patients with anti-IgA antibodies; non-dihydropyridine CCBs (diltiazem, verapamil) in CVID with cardiac involvement.

DxTest of choiceSerum immunoglobulins (IgG, IgA, IgM, IgE) plus vaccine response testing (pneumococcal polysaccharide + protein antigens) plus B-cell immunophenotyping (switched memory B cells, CD21low B cells).

ScKey scoreEUROclass classification (smB <2% = high risk; CD21low >10% = lymphoproliferation) and clinical phenotype (infection-only vs complicated CVID).

→When to referRefer to immunology at diagnosis; consider specialized center for complicated CVID (non-infectious complications, monogenic defect, refractory disease, need for HSCT or targeted biologic).

CVID is the most common primary immunodeficiency in adults, driven by humoral and T-cell defects. Early immunoglobulin replacement reduces infections, but non-infectious complications (autoimmune cytopenias, lymphoproliferation, GLILD, malignancy) determine prognosis and require targeted immunosuppression. Monogenic causes guide therapy, and systematic surveillance improves outcomes.

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency in adults, characterized by low serum immunoglobulins (IgG and IgA and/or IgM) and impaired specific antibody responses. The disease manifests with recurrent sinopulmonary infections, autoimmune cytopenias, lymphoproliferation, enteropathy, and increased malignancy risk, complications that now dominate morbidity and mortality. Diagnostic delays of 5-8 years are common. Early immunoglobulin replacement therapy reduces infection frequency and improves survival; effective management requires parallel strategies for infectious prophylaxis and targeted immunosuppression for non-infectious complications. This overview synthesizes the current paradigm for evaluation and management.

Overview and Recommendations

Background

•CVID is the most common symptomatic primary immunodeficiency in adults, with an estimated prevalence of 1 in 500 to 1 in 500,000. It is defined by low serum IgG and low IgA (with or without low IgM) and defective specific antibody production, leading to recurrent infections and immune dysregulation that spans B- and T-cell compartments.
•The classic presentation involves recurrent sinopulmonary infections (pneumonia as first manifestation in 32% of patients), but non-infectious complications, autoimmune cytopenias (ITP, AIHA, Evans syndrome), lymphoproliferation (splenomegaly, lymphadenopathy), enteropathy, granulomatous-lymphocytic interstitial lung disease (GLILD), and malignancy, now drive most morbidity. The presence of even one non-infectious complication confers an 11-fold increase in mortality compared with infection-only disease.
•Pathophysiology centers on a fundamental B-cell maturational defect (reduced class-switched memory B cells) compounded by T-cell dysregulation: follicular helper T-cell expansion, regulatory T-cell deficiency, and chronic innate immune activation driven by microbial translocation. IgA deficiency with impaired anti-LPS antibodies permits endotoxemia, which triggers a BTK-dependent proinflammatory cytokine cascade (TNF-α, IL-6, IFN-γ, CXCL9, CXCL10) in genetically susceptible individuals.
•Monogenic causes are identified in 20-30% of patients, most commonly heterozygous loss-of-function variants in (4% of Europeans), haploinsufficiency, deficiency, and defects in , , , and . Identification of a specific genetic defect can guide targeted therapy (e.g., abatacept for CTLA-4 insufficiency, sirolimus for LRBA deficiency) and consideration of hematopoietic stem cell transplantation.
•Diagnostic criteria per ESID/ICON require onset after age 2 years, low IgG and low IgA (and/or low IgM), impaired vaccine responses to pneumococcal polysaccharide and protein antigens, and exclusion of secondary causes of hypogammaglobulinemia. Patients are clinically stratified into infection-only (CVIDio) and complicated CVID (CVIDc), the latter encompassing autoimmune, lymphoproliferative, enteropathic, and malignant phenotypes, to guide prognosis and surveillance intensity.

Evaluation

•Suspect CVID in any adult with recurrent sinopulmonary infections (≥2 pneumonias in 1 year, chronic sinusitis, otitis media), especially when accompanied by unexplained autoimmune cytopenia, splenomegaly, lymphadenopathy, chronic diarrhea, or bronchiectasis.
•Ask about age at first serious infection, frequency of antibiotic courses, history of pneumonia, bronchiectasis, autoimmune disease (ITP, AIHA, Evans syndrome), family history of immunodeficiency, and prior immunoglobulin measurements. Diagnostic delay averages 5-8 years, so maintain a low threshold.
•Examine for signs of chronic lung disease (crackles, clubbing), lymphadenopathy, splenomegaly, mucocutaneous candidiasis, and skin findings (vitiligo in 8.5%, eczema in 22.4%, purpura from thrombocytopenia).
•Order initial laboratory workup: complete blood count with differential, serum immunoglobulins (IgG, IgA, IgM, IgE), and serum protein electrophoresis with calculated globulin (CG <22 g/L has 80% sensitivity, 87% specificity for hypogammaglobulinemia). Low IgG and low IgA are required for diagnosis.
•Evaluate specific antibody responses by measuring pre- and 4-week post-vaccination titers to pneumococcal polysaccharide (Pneumovax) and protein antigens (tetanus, diphtheria). Failure to achieve a ≥2-fold rise or protective levels in <70% of serotypes defines the defect. If the patient is already on IVIG, use ELISPOT assay for antibody-secreting cells instead of serology.
•Perform B-cell immunophenotyping by flow cytometry: quantify switched memory B cells (CD27+IgD-), marked reduction (<2% of B cells) is a hallmark of CVID and predicts non-infectious complications. Expansion of CD21low B cells (>5% of B cells) correlates with GLILD and splenomegaly.
•Assess T-cell subsets: low naive CD4+ T cells (<20% of total CD4+) defines late-onset combined immunodeficiency (LOCID), which independently predicts splenomegaly, lymphadenopathy, interstitial lung disease, lymphoma, and shortened survival.
•Consider serum B-cell maturation antigen (sBCMA) as a novel biomarker: <15 ng/mL has 97% positive predictive value for CVID or X-linked agammaglobulinemia; ≥25 ng/mL has 88% negative predictive value.
•Genetic testing (targeted gene panel or whole exome) is indicated for patients with non-infectious complications dominating the phenotype, family history of immunodeficiency, or severe/atypical infections. Identification of a monogenic cause (NFKB1, CTLA4, LRBA, etc.) can direct targeted therapy and cascade screening of relatives.
•In patients with atopic symptoms but negative skin prick testing or serum specific IgE, consider bronchial challenge to confirm allergic asthma, as standard allergy testing is often falsely negative in CVID (only 9.7% have atopy by skin test despite suggestive histories).
•Rule out secondary causes of hypogammaglobulinemia: medications (rituximab, anticonvulsants, sulfasalazine), protein-losing enteropathy, nephrotic syndrome, lymphoproliferative diseases (CLL, thymoma/Good syndrome), and chronic infections (HIV, EBV, CMV).
•Perform baseline screening for established complications: high-resolution chest CT (HRCT) to assess for bronchiectasis and GLILD, pulmonary function tests including FVC and DLCO, and upper endoscopy with standardized biopsies to screen for atrophic gastritis and intestinal metaplasia (found in 34% of CVID patients) if gastrointestinal symptoms are present.
•Refer to an immunologist for confirmation and initiation of immunoglobulin replacement therapy; coordinate a multidisciplinary approach including pulmonology, gastroenterology, and hematology for complicated cases.

Management

•Initiate immunoglobulin replacement therapy (IgRT) as soon as the diagnosis is confirmed. Start 400-600 mg/kg every 3-4 weeks or 100-200 mg/kg weekly; titrate the dose to maintain a trough IgG >700-800 mg/dL, though the ideal level should be individualized based on breakthrough infection frequency.
•SCIG is increasingly preferred for its flexibility, fewer systemic adverse effects, suitability for home administration, and improved quality of life. IVIG remains appropriate for patients who prefer center-based therapy or have adherence concerns.
•For breakthrough sinopulmonary infections despite adequate trough IgG levels, add antimicrobial prophylaxis: one double-strength tablet daily or 250 mg three times weekly. Tailor choice based on sputum culture results when possible.
•Manage GLILD with high-dose corticosteroids: initiate at ≥0.3 mg/kg daily (or equivalent). This regimen improves HRCT scores and forced vital capacity, achieving durable remission in approximately 42% of patients. Low-dose maintenance (<0.3 mg/kg) provides no added benefit, taper to the lowest effective dose over 4-8 weeks.
•For steroid-refractory or relapsing GLILD, use -based therapy. Low-dose rituximab 150 mg/m² weekly may achieve remission with fewer infections; standard-dose rituximab 375 mg/m² every 3 weeks is an alternative but carries a higher risk of opportunistic infections. Combination with azathioprine (dose per protocol) has shown benefit in case series.
•For autoimmune cytopenias (ITP, AIHA, Evans syndrome), first-line treatment is high-dose corticosteroids (e.g., pulse therapy). For refractory cases, consider rituximab, azathioprine, or other steroid-sparing immunosuppressants. Maintain IgG trough >7 g/L to reduce autoimmune thrombocytopenia episodes.
•In monogenic CVID due to haploinsufficiency, administer abatacept (CTLA-4 fusion protein) as targeted therapy. Hematopoietic stem cell transplantation (HSCT) can achieve sustained remission in 72% of CTLA-4 mutation carriers and is also an option for severe deficiency or other monogenic defects with refractory immune dysregulation.
•For LRBA deficiency, (mTOR inhibitor) has demonstrated efficacy in reducing lymphoproliferation and autoimmunity; consider HSCT if disease is severe and progressive.
•For refractory chronic spontaneous urticaria in CVID, can induce complete remission after the first injection and is well tolerated over 12 months.
•For malignancy arising in CVID (e.g., lung adenocarcinoma, lymphoma), (nivolumab, pembrolizumab) have been used successfully, achieving partial response with progression-free survival >15 months. Do not automatically exclude CVID patients from checkpoint inhibitor trials.
•Vaccination: administer inactivated influenza vaccine annually and mRNA vaccine series with boosters as recommended. Humoral responses develop in 52-83% of CVID patients but wane rapidly; T-cell responses are more durable and correlate with protection against severe disease. Live vaccines are contraindicated.
•Monitor for complications systematically: perform annual pulmonary function tests; repeat HRCT every 1-2 years if GLILD is present (consider MRI as radiation-sparing alternative); screen for gastric cancer with baseline upper endoscopy and standardized biopsies at diagnosis, then every 3-5 years (especially in smokers or with H. pylori infection).
•Intubation criteria for acute respiratory failure: FVC <20 mL/kg ideal body weight, PaO2/FiO2 ratio <150 mm Hg on non-rebreather, hypercapnia (PaCO2 >50 mm Hg with pH <7.30), or signs of impending fatigue (accessory muscle use, respiratory rate >35 breaths/min, abdominal paradox).
•Provide standard VTE prophylaxis for hospitalized CVID patients: 40 mg SC daily or 5000 U SC twice daily, unless bleeding risk from severe thrombocytopenia or active bleeding.
•Refer patients with complicated CVID (non-infectious complications, monogenic defect, refractory disease) to specialized immunology/transplant centers for consideration of targeted biologic therapies or HSCT.
•In pregnancy, continue IgRT to maintain trough IgG >500-700 mg/dL; IVIG is safe with no moderate/severe adverse effects. Coordinate multidisciplinary care with maternal-fetal medicine, immunology, and neonatology. Breastfeeding is encouraged as colostrum contains protective antibodies against enteropathogenic E. coli.
•In elderly patients, individualize IgG trough targets to balance infection prevention against volume overload; SCIG may be preferred to avoid hemodynamic stress of IVIG. Monitor for comorbidities (chronic lung disease, diabetes, hypertension) that complicate management.
•Avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) as they exacerbate heart failure in patients with cardiac involvement. Avoid IgA-containing immunoglobulin products in patients with known anti-IgA antibodies at risk of anaphylaxis.
•Monitor for iatrogenic complications: corticosteroids increase opportunistic infection risk (2 cases in one series); rituximab may worsen humoral deficiency (compensated by IgRT); checkpoint inhibitors can trigger immune-related adverse events. Adjust immunosuppression in collaboration with the primary immunologist.

Board Review — High Yield

•Low IgG + IgA + impaired vaccine responses, Diagnostic triad for CVID; require onset after age 2 and exclusion of secondary causes.
•EUROclass smB- group, Switched memory B cells <2% of total B cells predicts splenomegaly, granulomatous disease, and lymphoma.
•CVIDc (complicated CVID), Presence of any non-infectious complication (cytopenias, lymphoproliferation, enteropathy) increases mortality 11-fold.
•NFKB1 haploinsufficiency, Most common monogenic cause (4% of Europeans); causes progressive B-cell defect, autoimmunity, and bronchiectasis.
•GLILD, Granulomatous-lymphocytic interstitial lung disease; diagnosed by HRCT + biopsy; treated with high-dose corticosteroids (≥0.3 mg/kg prednisone) ± rituximab.
•IVIG vs SCIG, Both first-line; SCIG has fewer systemic reactions and enables home therapy; target trough IgG >700-800 mg/dL.
•CTLA-4 insufficiency, Responds to abatacept; HSCT can be curative.
•Vaccination in CVID, Humoral responses blunted (52-83% seroconversion to COVID-19 mRNA vaccine, rapid waning); T-cell responses more durable; live vaccines contraindicated.
•Diagnostic delay, Averages 5-8 years; maintain high index of suspicion in adults with recurrent infections + autoimmunity or lymphoproliferation.
•Anaphylaxis risk, FCGR2A gain-of-function variant predisposes to IVIG reactions; switch to SCIG or use IgA-depleted products.

Deep Dive — Evidence Details

Definition, Classification & Immunodeficiency Defect Type

▸CVID is the most common symptomatic primary immunodeficiency in adults, defined by low immunoglobulins and impaired antibody responses.
▸Classification into infection-only (CVIDio) and complicated (CVIDc) phenotypes stratifies prognosis, with CVIDc carrying higher mortality from autoimmune, lymphoproliferative, and malignant complications.
▸Monogenic causes account for 20-30% of cases; NFKB1 loss-of-function is the most common in Europeans, but many patients lack an identifiable genetic variant.

HY High Yield: CVIDc is associated with TH1 polarization, expansion of cytotoxic CD4 TFH cells in lymph nodes, and defective germinal center formation [1,12].

Common Variable Immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency in adults, defined by low serum immunoglobulins (IgG and IgA and/or IgM) and impaired specific antibody responses, leading to recurrent infections, autoimmunity, lymphoproliferation, and increased malignancy risk ^[25]^D5.

Also Called: CVID, common variable immunodeficiency disorder, late-onset hypogammaglobulinemia.

Hypersensitivity Classification: CVID is not classified under the Gell-Coombs hypersensitivity schema. It is a primary immunodeficiency of humoral immunity, driven by defective B-cell differentiation and function. Many patients also exhibit T-cell dysregulation, including TH1 polarization ^[1]^C4 and expansion of a cytotoxic CD4 TFH-cell cluster in lymph nodes ^[12]^B3b, which accounts for the frequent autoimmune and inflammatory complications. Thus, CVID is best framed as a primary immunodeficiency involving both B- and T-cell compartments.

Clinical Phenotypes

The European Society for Immunodeficiencies (ESID) registry provides diagnostic criteria ^[15]^D5. Patients are broadly categorized into infection-only (CVIDio) and complicated CVID (CVIDc) ^[16]^B3b^[32]^C4.

Phenotype	Key Features	Clinical Implication
Infection-only	Recurrent sinopulmonary infections; no autoimmune or lymphoproliferative complications	Lower mortality; better prognosis ^[16]^B3b
Complicated (CVIDc)	Autoimmune cytopenias, lymphoproliferation (splenomegaly, lymphadenopathy), granulomatous disease, enteropathy	Higher mortality from infections and neoplasia; requires targeted immunosuppression ^[16]^B3b
Monogenic subtypes	Pathogenic variants in NFKB1 (most common in Europeans), CTLA4, LRBA, NFKB2, PIK3CD, TACI, BAFFR, CD19, ICOS, TRAF3, RAG2, IRF2BP2	Often autosomal dominant with variable penetrance; may guide therapy (e.g., CTLA-4 fusion protein) ^[6]^C4^[11]^C4^[17]^D5^[26]^C4^[30]^C4^[35]^D5^[37]^C4

Genetic Architecture: A monogenic cause is identified in approximately 20-30% of patients, most commonly heterozygous loss-of-function NFKB1 variants (4% of European CVID) ^[11]^C4^[27]^C4. These defects converge on impaired germinal center formation and B-cell class-switch recombination.

Clinical Significance: CVID carries substantial morbidity. Hepatic complications occur in 10% of hospitalizations and increase in-hospital mortality from 4% to 11% ^[19]^C4. Premature death is driven by infections and malignancy, particularly in CVIDc patients with lymphopenia, thrombocytopenia, or elevated liver enzymes ^[16]^B3b. Early immunoglobulin replacement therapy reduces infection frequency and improves survival ^[34]^C4.

Pearl: CVID is not a hypersensitivity disorder but a primary humoral immunodeficiency with frequent T-cell dysregulation; categorizing patients as infection-only versus complicated CVID (CVIDc) stratifies prognosis - CVIDc carries a higher risk of mortality from autoimmune and lymphoproliferative complications, and should trigger a thorough search for monogenic causes ^[6]^C4^[11]^C4^[16]^B3b.

Pathophysiology & Immune Mechanism

▸CVID is a heterogeneous antibody-deficiency syndrome in which a substantial subgroup develops immune dysregulation and chronic inflammation. [83][238][244]
▸CD21low B-cell expansion, T-bet-high CD21low B cells, IL-10, and altered T-cell/monocyte profiles are linked to complicated CVID. [83][242][245]
▸CD57+ CD8+ T-cell expansion is associated with granuloma or lymphadenopathy and CMV positivity in CVID. [239]
▸Tryptophan–kynurenine metabolism and gut dysbiosis are candidate contributors to inflammatory CVID phenotypes, but association does not establish causality. [9]
▸Monogenic disorders including NFKB1 haploinsufficiency, hypomorphic IL2RG variants, IRF2BP2 deficiency, and STAT3 gain-of-function can produce CVID-like disease. [40][44][47][246]

Dx Diagnostic Essentials: Persistent inflammation, lymphoproliferation, unusual infections, marked T-cell abnormalities, or atypical organ disease should prompt genetic testing or reassessment for a monogenic CVID-like disorder rather than assuming a nonspecific CVID mechanism. [44][240]

! Warning: Findings from CTLA4 deficiency, Good syndrome, CAR-T-associated injury, autoimmune enteropathy, or hereditary angioedema provide differential or mechanistic context and should not be directly attributed to CVID without disease-specific evidence. [54][81][236][237][243]

Core immunobiology

Common variable immunodeficiency (CVID) is a heterogeneous inborn error of immunity in which impaired antibody production coexists, in a clinically important subgroup, with dysregulated cellular immunity and chronic inflammation. The inflammatory phenotype is commonly described as complicated CVID (CVIDCOMP/CVIDc), and is associated with autoimmune, autoinflammatory, granulomatous, lymphoproliferative, gastrointestinal, hepatic, and pulmonary complications. ^[83]^B3b^[238]^[244] Autoimmune or autoinflammatory manifestations are not restricted to patients with a previously established immunodeficiency diagnosis; in a large inborn-error-of-immunity cohort, these complications were present in 26.3% of patients and were the initial presentation in nearly half of affected individuals. ^[238]

The immune defect is therefore not simply quantitative hypogammaglobulinemia. CVID can involve altered T-cell and monocyte/macrophage homeostasis, abnormal B-cell differentiation, persistent immune activation, and defective coordination between adaptive and innate responses. ^[9]^C4^[83]^B3b^[239] Expansion of CD21low B cells is a recognized immunophenotypic feature of the immune-dysregulatory subgroup, particularly alongside chronic type 1 immune activation. ^[242] A related population, T-bet-high CD21low B cells, is associated with increased circulating and tissue IL-10; IL-10-producing cells include monocytes, T cells, and a subset of CD21low B cells. ^[245]^D These findings support a model in which compensatory or chronically stimulated immune-cell states may themselves participate in persistent inflammation rather than merely reflect antibody deficiency. ^[242]^[245]^D

T-cell, monocyte, and cytokine dysregulation

T-cell pathology is prominent in inflammation-prone CVID. An exploratory transcriptomic and proteomic study of isolated CD3+ T cells and CD14+ monocytes identified broader molecular alterations in CVID patients with autoimmune and inflammatory complications than in healthy controls, supporting cell-intrinsic abnormalities in both lymphoid and myeloid compartments. ^[83]^B3b The same study measured IL-1β, CXCL10, IL-18, and CXCL9 as candidate inflammatory mediators, indicating that inflammasome-, interferon-, and chemokine-linked pathways are being investigated as components of CVIDCOMP biology; the available abstract does not establish that each mediator is uniformly elevated in all patients. ^[83]^B3b

Serum cytokine profiling has also been evaluated as a potential surrogate for flow-cytometric identification of complicated CVID, particularly where access to lymphocyte-subset testing is limited. ^[244] This supports the clinical concept that systemic cytokine patterns may reflect immune dysregulation, but cytokine testing should not be interpreted as a universal replacement for cellular phenotyping because the study assessed diagnostic utility retrospectively. ^[244]

Expansion of terminally differentiated or senescent-like CD57+ CD8+ T cells has been specifically investigated in CVID. This population has been associated with granuloma or lymphadenopathy and with cytomegalovirus (CMV) positivity, linking chronic antigenic stimulation or viral latency with altered cytotoxic T-cell homeostasis. ^[239] CMV latency may also shape antigen-specific cellular immunity: in predominantly antibody-deficient patients with inborn errors of immunity, vaccine-induced CD4+ T-cell responses were evaluated together with CMV-specific responses, demonstrating the importance of viral history when interpreting cellular immune function. ^[235]^B2c

Metabolic and microbiome-associated inflammation

The tryptophan–kynurenine pathway is a candidate bridge between chronic immune activation, monocyte/T-cell biology, and intestinal microbial imbalance in CVID. A 2025 study measured pathway metabolites and neopterin in CVID cohorts specifically to test relationships with inflammatory and immunologic phenotypes and gut dysbiosis. ^[9]^C4 These data support investigation of immunometabolism as a disease-modifying axis, but metabolite associations should not be treated as proof of causality. ^[9]^C4

Microbial ecology may also influence immune-dysregulatory disease. In CTLA4 deficiency, a related inborn error of immune regulation characterized by regulatory T-cell dysfunction and intestinal immune infiltration, Veillonella and Streptococcus were identified as microbiome biomarkers distinguishing affected individuals from healthy cohorts. ^[236]^C Because CTLA4 deficiency is genetically and mechanistically distinct from most CVID, these findings are mechanistic context rather than direct evidence that the same organisms cause CVID. ^[236]^C

Genetic heterogeneity and CVID-like disease

Some patients labelled as having CVID have monogenic disorders that produce a CVID-like phenotype, making genetic testing important for mechanism-based classification and treatment selection. ^[44]^C4 Examples include NFKB1 haploinsufficiency, caused by monoallelic loss-of-function variants and associated with hypogammaglobulinemia or a CVID-like phenotype; in one Japanese series, clinical penetrance was 52%, illustrating variable expression even within a defined genetic disorder. ^[246]^D Hypomorphic IL2RG variants can produce adult-onset antibody deficiency with moderate CD4+ T-cell lymphopenia rather than classic severe combined immunodeficiency, demonstrating that partial cytokine-receptor dysfunction can present along a CVID spectrum. ^[40]^C4 IRF2BP2 variants have likewise been investigated as a form of CVID with inflammation through clinical and functional studies of 34 individuals from 18 families. ^[47]^C4

STAT3 gain-of-function disease may be diagnosed after years of a CVID label and can redirect therapy toward the underlying pathway, emphasizing that persistent inflammation, unusual infections, or atypical lymphoproliferation should prompt genetic reassessment. ^[44]^C4 Automated flow-cytometry analysis incorporating lymphocyte profiles, age, and immunoglobulin levels is being developed to improve screening for lymphoid primary immunodeficiencies, but such tools assist rather than replace clinical and molecular diagnosis. ^[240]

Mechanistic boundaries and differential context

Gastrointestinal villous atrophy and chronic diarrhea can arise in both CVID and autoimmune enteropathy, reflecting overlapping consequences of immune-mediated intestinal injury but requiring clinicopathologic discrimination. ^[243] Good syndrome is a separate adult-onset immunodeficiency associated with thymoma, hypogammaglobulinemia, and combined B- and T-cell defects; it should not be assumed to represent CVID biology. ^[81]^C4 Similarly, hereditary angioedema and CVID can coexist and produce overlapping gastrointestinal or treatment-related diagnostic confusion without sharing the same immune mechanism. ^[54]^C4 Histologic gastrointestinal injury after CAR-T-cell therapy or anti-CD38 treatment represents an acquired treatment-associated context and is not evidence for CVID pathogenesis. ^[237]^C

Finally, impaired humoral responses do not imply absent cellular immunity. Across heterogeneous inborn errors of immunity, repeated SARS-CoV-2 vaccination studies found lower antibody responses but measurable or enhanced T-cell responses in some cohorts, including patients with CVID; individual responses remain variable. ^[241]^C^[67]^B2b Thus, CVID pathophysiology is best understood as a spectrum combining defective antibody generation with context-dependent T-cell, B-cell, myeloid, cytokine, metabolic, microbial, and genetic abnormalities. ^[9]^C4^[83]^B3b^[242]^[245]^D

Mechanistic domains implicated in complicated CVID

Domain	Evidence and interpretation
B-cell dysregulation	Expansion of CD21low and T-bet-high CD21low B cells, with IL-10 production by multiple immune-cell sources. ^[242]^[245]^D
T-cell dysregulation	CD57+ CD8+ T-cell expansion and broader molecular abnormalities in T cells from CVID patients with inflammatory complications. ^[83]^B3b^[239]
Myeloid and cytokine activation	Altered CD14+ monocyte profiles and investigation of IL-1β, IL-18, CXCL9, and CXCL10; serum cytokines may aid complication phenotyping. ^[83]^B3b^[244]
Immunometabolism and microbiome	Tryptophan–kynurenine metabolites, neopterin, and gut dysbiosis are being evaluated as correlates of inflammation; CTLA4-deficiency microbiome findings provide related mechanistic context. ^[9]^C4^[236]^C
Genetic heterogeneity	NFKB1, IL2RG, IRF2BP2, and STAT3 pathway defects can create CVID-like or inflammatory phenotypes with variable penetrance. ^[40]^C4^[44]^C4^[47]^C4^[246]^D

Epidemiology, Etiology & Risk Factors

▸CVID is heterogeneous; referral cohorts show prominent respiratory infection, gastrointestinal disease, and autoimmunity. [29]
▸Māori patients in New Zealand were reported to have high prevalence of bronchiectasis and complete IgA deficiency, but the supplied evidence does not provide comparative prevalence estimates. [253]
▸Compared with CVID, isolated IgG, IgG-subclass, and combined IgG/IgM deficiencies generally showed fewer respiratory or gastrointestinal infections but more mucocutaneous herpes simplex reactivation. [103, 249]
▸Immune dysregulation, including autoimmune cytopenias, splenomegaly, granulomatous or lymphoproliferative disease, enteropathy, and liver involvement, contributes substantially to CVID heterogeneity. [16, 29, 94, 102, 239]
▸Gut microbiome and tryptophan–kynurenine findings are investigational and do not yet establish causal risk factors for CVID severity. [9, 236]
▸Infection and complication risk is influenced by phenotype, comorbidity, age, IgG trough concentration, and the distinction between primary and secondary hypogammaglobulinemia. [94, 101, 247, 250]

CP Clinical Pearl: CVID-like presentations with prominent autoimmunity, lymphoproliferation, enteropathy, or cytopenias warrant consideration of defined immune-dysregulation disorders, including CTLA4-related disease, while recognizing that the cited microbiome evidence is not CVID-specific. [16, 102, 236, 239]

! Warning: Most prevalence figures cited from IEI registries or tertiary referral cohorts cannot be extrapolated directly to the general CVID population. [29, 97, 101, 238, 252, 253]

Epidemiology and clinical spectrum

Common variable immunodeficiency (CVID) is a heterogeneous primary antibody-deficiency disorder characterized by impaired immunoglobulin production and clinically significant infection susceptibility. In a 10-year Indian tertiary-center cohort of 150 patients, the median age at diagnosis was 18 years, 62% were male, and 66.6% had a severe phenotype; recurrent respiratory tract infection was the most frequent manifestation (84.2%), followed by gastrointestinal complications (45%) and autoimmune manifestations (21%). ^[29]^C4 These findings describe a referral population and should not be interpreted as population prevalence estimates. ^[29]^C4

The New Zealand CVID Study enrolled 108 patients, representing approximately 70% of patients with known CVID in New Zealand, and reported marked ethnic variation in disease prevalence and sequelae; the Māori population was specifically associated with a high prevalence of bronchiectasis and complete IgA deficiency. ^[253]^C The abstract does not provide the corresponding prevalence estimates or comparative denominators, so the magnitude and cause of this disparity remain uncertain. ^[253]^C

CVID is clinically distinct from isolated IgG deficiency, IgG-subclass deficiency, and combined IgG/IgM deficiency. Compared with CVID, isolated IgG or combined IgG/IgM deficiency was associated with fewer respiratory and gastrointestinal infections, whereas recurrent mucocutaneous herpes simplex reactivation was more frequent; splenomegaly and immune thrombocytopenic purpura were more common in CVID. ^[249] In a separate cohort comparing 96 patients with IgG-subclass deficiency with 270 patients with CVID, recurrent lower-respiratory-tract infection and bronchiectasis were less common in IgG-subclass deficiency, while recurrent mucocutaneous herpes simplex reactivation was more common; arthritis was associated with IgG-subclass deficiency, whereas autoimmune cytopenias were more characteristic of CVID. ^[103]^B3b

Etiology and biological heterogeneity

CVID represents a biologically heterogeneous group of disorders rather than a single molecular disease. The supplied studies evaluate immune dysregulation, cellular phenotypes, metabolites, and host–microbiome interactions, but do not establish a single causal pathway for most patients. ^[9]^C4^[83]^B3b^[239]

A clinically important subgroup has immune-dysregulation complications, including autoimmunity, inflammatory disease, granulomatous or lymphoproliferative manifestations, enteropathy, and liver disease. ^[16]^B3b^[29]^C4^[94]^B2b^[102]^B3b^[239] Expansion of CD57-positive CD8 T cells has been investigated as an immune phenotype in CVID and was associated with granuloma/lymphadenopathy and positive cytomegalovirus status in the reported cohort. ^[239] An exploratory transcriptomic and proteomic study found broader molecular changes in T cells and monocytes from patients with autoimmune/inflammatory CVID complications than in controls, supporting T-cell and monocyte pathology as a potential contributor to the inflammatory phenotype. ^[83]^B3b

The tryptophan–kynurenine pathway has also been studied as a possible link between immune activation and intestinal microbial disturbance in CVID. The investigation measured pathway metabolites and neopterin in a discovery cohort of 40 patients, with analyses of clinical and immunologic phenotype and gut dysbiosis. ^[9]^C4 The supplied abstract does not report the direction or effect size of the observed associations; therefore, these metabolites should be regarded as investigational biomarkers rather than established causal risk factors. ^[9]^C4

Gut microbial alterations may contribute to variable disease severity in selected immune deficiencies. In heterozygous cytotoxic T-lymphocyte-associated protein 4 deficiency (CTLA4-D)—a distinct inborn error of immunity characterized by regulatory T-cell dysfunction, intestinal immune-cell infiltration, immune dysregulation, and autoimmunity—the genera Veillonella and Streptococcus emerged as candidate microbiome biomarkers distinguishing affected individuals from healthy cohorts. ^[236]^C CTLA4-D should not be equated with CVID, although CTLA4-related disease may enter the differential diagnosis of CVID-like hypogammaglobulinemia and immune dysregulation. ^[236]^C

Risk factors for complications

The principal clinical risk pattern is the combination of impaired antibody production and immune dysregulation. In adults with CVID, gastrointestinal and hepatic manifestations may affect up to one-third of patients; a Spanish tertiary-center study evaluated enteropathy and liver involvement as prognostic factors for survival, gastrointestinal infection, and gastrointestinal cancer. ^[102]^B3b In a prospective stool-screening study of immunoglobulin-treated hypogammaglobulinemic patients, 73 individuals provided 111 samples; 53 had primary hypogammaglobulinemia, including 32 with CVID, and 20 had secondary hypogammaglobulinemia. The study specifically addressed Campylobacter carriage or infection risk in this population. ^[250]^C

Infection risk extends beyond routine respiratory disease. Among 10,004 patients in the French inborn-errors-of-immunity registry, 149 (approximately 1.4%) had at least one parasitic infection and 41 (27.5% of those with parasitic infection; 0.41% of the total registry) had cryptosporidiosis; the largest diagnostic category was combined immunodeficiency, so these figures are not CVID-specific. ^[101]^B3b In a cohort of 117 adults with inborn errors of immunity, tuberculosis exposure, symptoms, tuberculin skin testing, repeat testing when initially negative or minimally reactive, and chest imaging were evaluated; these data support exposure history and clinical context as important modifiers of tuberculosis risk assessment in IEI, but the supplied abstract does not provide CVID-specific rates. ^[248]^C

Noninfectious complications are also relevant to long-term risk. Across Algerian and Moroccan IEI registries, autoimmune or autoinflammatory manifestations occurred in 26.3% of 825 patients and autoimmune manifestations in 14.0% of 769 pediatric patients, respectively; these estimates include multiple IEI diagnoses and are not CVID prevalence estimates. ^[238]^[252] Malignancy has been reported in adult IEI cohorts, and a study of 355 adults evaluated malignancy prevalence and associated clinical, laboratory, immunologic, and genetic features. ^[97]^C4 Separately, patients with primary immunodeficiency were compared with the general population for head and neck cancer incidence using TriNetX and SEER data, although the supplied abstract does not state the effect estimates. ^[108]^B3b

Age and comorbidity may modify complication risk. In a multicenter study of 367 adults with CVID, chronic kidney disease was identified in 23 patients (6.27%) and was associated with older age, hypertension, diabetes, dyslipidemia, abnormal renal ultrasonography, and predominant intravenous immunoglobulin use. ^[94]^B2b Immunoglobulin replacement remains central to infection prevention; a 2025 dose-reduction study selected adults with humoral PID who had maintained IgG trough levels of at least 700 mg/dL, or 900 mg/dL under specified conditions, and had no significant infection during the preceding six months, indicating that baseline infection burden and IgG trough concentration are practical determinants of treatment-related risk assessment. ^[247]^C Local adverse reactions to subcutaneous immunoglobulin were investigated using clinical, anatomical, psychosocial, and geographic variables in a multicenter Spanish registry, but the supplied abstract does not identify definitive independent predictors. ^[251]

Selected epidemiologic and complication data

Population or study	Key finding
Indian CVID cohort, n=150	Median diagnosis age 18 years; 62% male; 84.2% recurrent respiratory infections; 45% gastrointestinal complications; 21% autoimmunity. ^[29]^C4
New Zealand CVID Study, n=108	Approximately 70% of known New Zealand CVID patients; Māori patients had high prevalence of bronchiectasis and complete IgA deficiency. ^[253]^C
Adult CVID kidney study, n=367	Chronic kidney disease in 23 patients (6.27%); associated with older age, hypertension, diabetes, dyslipidemia, abnormal ultrasound, and predominant IVIg use. ^[94]^B2b
French IEI registry, n=10,004	Cryptosporidiosis in 41 patients (0.41%); figures were not CVID-specific. ^[101]^B3b
Adults with humoral PID receiving SCIg	Dose-reduction eligibility included IgG trough ≥700 mg/dL, or ≥900 mg/dL in specified circumstances, and no significant infection for six months. ^[247]^C

Clinical Presentation

▸Recurrent respiratory tract infection is the predominant infectious presentation, occurring in 84.2% of one 150-patient cohort. [29]
▸Gastrointestinal complications occurred in 45% of the Indian cohort, while gastrointestinal or hepatic disease may affect up to approximately one-third of patients overall. [29][102]
▸Autoimmune and/or autoinflammatory disease may be the initial manifestation; it occurred in 26.3% of a large IEI cohort and was the initial presentation in nearly half of affected patients. [238]
▸Splenomegaly, immune thrombocytopenia, lymphoproliferation, and severe or unusual infections should prompt evaluation for a monogenic CVID-like disorder. [249][44]
▸Chronic diarrhea with villous atrophy requires differentiation of CVID-associated enteropathy from autoimmune enteropathy. [243]

Dx Diagnostic Essentials: A CVID-like presentation with severe or unusual infection, prominent autoimmunity, lymphoproliferation, or systemic inflammation warrants genetic testing for monogenic inborn errors of immunity. [37][38][44][120]

! Warning: Do not attribute chronic diarrhea, villous atrophy, liver disease, or nephrotic syndrome automatically to uncomplicated CVID; autoimmune enteropathy, CVID-associated liver disease, and AA amyloidosis are important alternative or consequential diagnoses. [102][119][243]

Overall phenotype

Common variable immunodeficiency (CVID) is a heterogeneous antibody-deficiency disorder characterized by impaired immunoglobulin production, recurrent infections, and immune dysregulation. ^[29]^C4 The clinical spectrum ranges from predominantly infectious disease to multisystem inflammatory, autoimmune, lymphoproliferative, gastrointestinal, hepatic, and malignant complications. ^[102]^B3b Diagnosis may occur in childhood or adulthood; in an Indian cohort of 150 patients, the median age at diagnosis was 18 years, and 62% were male. ^[29]^C4 In a Moroccan multicenter cohort, 61 patients were diagnosed according to ESID and MENA criteria, underscoring the continuing use of clinical and immunological criteria across diverse populations. ^[255]

Infectious presentation

Recurrent respiratory tract infection is the dominant presenting pattern. In the Indian cohort, 84.2% of patients had recurrent respiratory tract infections, and 66.6% had a severe clinical phenotype. ^[29]^C4 Respiratory infections may be accompanied by gastrointestinal infections, although their frequency varies according to the underlying hypogammaglobulinemia phenotype. Compared with CVID, isolated IgG deficiency and combined IgG/IgM deficiency were associated with fewer respiratory and gastrointestinal infections. ^[249] These distinctions are clinically relevant because patients with milder isolated or combined deficiencies may otherwise be classified incorrectly as having CVID. ^[249]

Patients with inborn errors of immunity, including antibody-predominant disorders, may require deliberate assessment for tuberculosis when epidemiological risk is present. A cohort study of 117 adults with inborn errors of immunity used exposure history, symptom assessment, tuberculin skin testing, repeat testing after 1–4 weeks when the initial induration was 0–4 mm, and chest radiography or computed tomography when available. ^[248]^C The study supports incorporating exposure and symptom review with immunological testing and chest imaging rather than relying on a single tuberculin result in immune-deficient adults. ^[248]^C Persistent or unusual infections should also prompt reconsideration of the diagnosis and genetic testing, because a longstanding CVID label may conceal a monogenic immune dysregulation disorder. ^[44]^C4

Gastrointestinal and hepatic manifestations

Gastrointestinal involvement is common and clinically important. In the Indian cohort, 45% of patients had gastrointestinal complications. ^[29]^C4 Up to approximately one-third of patients with CVID may develop gastrointestinal or hepatic manifestations, and objective CVID-associated enteropathy or liver involvement may be demonstrated clinically, endoscopically, histologically, radiologically, or by hemodynamic assessment. ^[102]^B3b Chronic diarrhea, malabsorption, weight loss, and small-intestinal villous atrophy can occur, but the differential includes autoimmune enteropathy. In a comparison of patients with gastrointestinal involvement, autoimmune enteropathy was associated with a shorter duration of severe diarrhea and greater weight loss than CVID. ^[243]

Liver disease may be clinically silent or detected through non-invasive assessment. A study of 22 patients with CVID and 9 with agammaglobulinemia evaluated hepatic involvement using the Enhanced Liver Fibrosis score and shear-wave elastography, reflecting the need to investigate liver disease even when fibrosis has not previously been documented. ^[136]^C4 Clinically significant chronic inflammation and recurrent infection may rarely lead to AA amyloidosis; one reported patient with CVID had recurrent pneumonia, chronic sinusitis, osteomyelitis, sepsis, repeated lower-respiratory infections, and subsequent nephrotic syndrome caused by biopsy-confirmed AA amyloidosis. ^[119]^C4

Autoimmunity, inflammation, and lymphoproliferation

Noninfectious manifestations are frequent. In the Indian cohort, autoimmune disease occurred in 21% of patients. ^[29]^C4 In a larger cohort of 825 patients with inborn errors of immunity, autoimmune and/or autoinflammatory manifestations occurred in 26.3%, and these findings were the initial clinical presentation in nearly half of affected patients. ^[238] Autoimmune cytopenias are particularly important: autoimmune thrombocytopenia is frequent in CVID, and in a prospective observational cohort of 47 adults with CVID and autoimmune immune thrombocytopenia, 25.5% experienced defined thrombocytopenic episodes during 64 months of follow-up. ^[234]^B2b

Splenomegaly and immune thrombocytopenic purpura were more frequent in CVID than in isolated IgG or combined IgG/IgM deficiency. ^[249] Lymphoproliferation and splenic abnormalities may therefore help distinguish CVID from milder antibody deficiencies. A newly described “sponge-like” splenic sonographic microtexture has been reported in patients with immune dysregulation disorders, although its diagnostic significance remains investigational. ^[36]^B3b

The inflammation-prone CVID phenotype is associated with abnormalities in T-cell and monocyte transcriptional and proteomic profiles, with reported changes involving inflammatory pathways and circulating mediators such as IL-1β, IL-18, CXCL9, and CXCL10. ^[83]^B3b Clinical manifestations may include autoimmune cytopenias, inflammatory disease, and organ-specific autoimmunity. For example, LRBA deficiency within the CVID spectrum may present with isolated chronic immune thrombocytopenia or progress to hemorrhagic complications and lymphoproliferation. ^[120]^C4 CTLA4 haploinsufficiency may resemble CVID while presenting with autoimmunity, inflammation, neoplasia, or infections, including severe cutaneous Pseudomonas infection, severe varicella-zoster virus infection, and Evans syndrome. ^[38]^C4

Phenotypic clues to alternative genetic diagnoses

Genetic testing is considered standard of care in newly diagnosed CVID because monogenic disorders can produce a CVID-like phenotype and may require directed therapy. ^[44]^C4 A diagnosis of STAT3 gain-of-function was ultimately made in a patient previously labeled as having CVID for more than 10 years; unusual infection, including nontuberculous lymphadenitis, helped prompt reassessment. ^[44]^C4 IRF2BP2 deficiency may cause hypogammaglobulinemia with reduced memory B cells, impaired plasmablast differentiation, Th1 polarization, and systemic inflammation, including primary biliary cholangitis and arthritis. ^[37]^C4 These findings illustrate that autoimmunity, lymphoproliferation, unusual infection, severe viral disease, or disproportionate inflammation should be considered clinical clues to a defined immune dysregulation syndrome rather than assumed to represent uncomplicated CVID. ^[37]^C4^[38]^C4^[44]^C4

Immunophenotypic and functional considerations

CVID may include cellular immune abnormalities in addition to defective antibody production. Flow-cytometric immune profiling can characterize altered lymphoid populations and integrate age and immunoglobulin levels to suggest lymphoid primary immunodeficiency subtypes; an explainable artificial-intelligence pipeline was developed for this purpose using standardized EuroFlow data. ^[240] Among predominantly antibody-deficient patients with inborn errors of immunity, antigen-specific T-cell responses after two doses of mRNA COVID-19 vaccine were assessed, with responses varying across patients and influenced by CMV latency. ^[235]^B2c Thus, the clinical phenotype should be interpreted alongside quantitative immunoglobulins, vaccine responses, lymphocyte subsets, memory B-cell and plasmablast assessment, and genetic findings. ^[37]^C4^[240]^[235]^B2c

Treatment-related clinical context

Immunoglobulin replacement is the cornerstone of infection prevention in CVID and may be administered intravenously or subcutaneously; both routes have similar overall efficacy, while subcutaneous treatment is associated with fewer systemic adverse events and greater patient autonomy. ^[254] Route of replacement does not eliminate the risk of immune complications: autoimmune thrombocytopenia has been observed in patients receiving both subcutaneous and intravenous immunoglobulin. ^[234]^B2b

Clinical patterns and diagnostic clues

Clinical pattern	Reported findings	References
Recurrent infection	Respiratory tract infections in 84.2% of an Indian CVID cohort; gastrointestinal infections are less frequent in isolated IgG or combined IgG/IgM deficiency than in CVID.	^[29]^C4^[249]
Gastrointestinal/hepatic disease	Gastrointestinal complications in 45% of one cohort; enteropathy and liver involvement may be objectively demonstrated by clinical, endoscopic, histologic, radiologic, or hemodynamic findings.	^[29]^C4^[102]^B3b
Autoimmunity	Autoimmune disease in 21% of one CVID cohort; autoimmune thrombocytopenia is frequent and defined episodes occurred in 25.5% of a prospective cohort.	^[29]^C4^[234]^B2b
Lymphoproliferation	Splenomegaly and immune thrombocytopenic purpura were more frequent in CVID than in isolated IgG or combined IgG/IgM deficiency.	^[249]
Red flags for genetic mimics	Unusual infections, severe viral disease, autoimmunity, inflammation, lymphoproliferation, or organ-specific disease may indicate STAT3 gain-of-function, CTLA4, LRBA, or IRF2BP2-related disease.	^[37]^C4^[38]^C4^[44]^C4^[120]^C4

Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup

▸Use quantitative IgG, IgA, and IgM together with clinical phenotype and functional antibody assessment to distinguish CVID from isolated IgG or combined IgG/IgM deficiency. [249]
▸Do not exclude allergic disease because of CVID or low IgE; allergy testing must be phenotype- and exposure-directed. [257]
▸Consider hereditary angioedema, drug reactions, mast-cell disorders, autoimmunity, and infection in patients labelled as having antibiotic or other immediate allergy. [54]
▸Include lymphocyte flow cytometry and consider cellular antigen-response testing when the phenotype suggests broader immune dysfunction. [240] [235]
▸Repeat a TST after 1–4 weeks when the initial result is 0–4 mm in an IEI tuberculosis-screening pathway. [248]
▸Pursue genetic testing in newly diagnosed, atypical, longstanding, or immune-dysregulated CVID-like disease. [44] [246] [38] [120]

Dx Diagnostic Essentials: A CVID label should trigger evaluation for immune dysregulation and monogenic CVID-like disorders, not only measurement of immunoglobulin concentrations. [44] [246] [38] [120]

CP Clinical Pearl: Allergic symptoms, antibiotic reactions, angioedema, and recurrent infection can overlap clinically; interpret allergy tests only after defining the phenotype and considering hereditary angioedema and other mimics. [54] [257]

Diagnostic scope

CVID should be evaluated as a heterogeneous antibody-deficiency phenotype rather than as a diagnosis based solely on recurrent infection. The workup should integrate quantitative immunoglobulins, functional antibody assessment, lymphocyte immunophenotyping, immune-dysregulation findings, exclusion of secondary hypogammaglobulinemia, and genetic investigation when clinically appropriate. Recent comparative data indicate that isolated IgG deficiency and combined IgG/IgM deficiency have generally fewer respiratory and gastrointestinal infections than CVID, whereas CVID more often has splenomegaly and immune thrombocytopenic purpura; recurrent mucocutaneous herpes simplex reactivation was more frequent in the non-CVID groups. These distinctions support repeat and comparative immune testing rather than automatic classification as CVID. ^[249]

Allergy assessment and interpretation

A careful history should distinguish immediate hypersensitivity, delayed drug reactions, recurrent infection, autoimmune disease, hereditary angioedema, and mast-cell disorders. Angioedema and antibiotic-associated symptoms may mimic allergy; a reported antibiotic hypersensitivity was ultimately diagnostically challenging in a patient with concurrent type I hereditary angioedema and CVID. ^[54]^C4 Therefore, testing should be guided by the reaction phenotype and timing rather than by the label of “allergy” alone. ^[54]^C4

Allergic disease is not excluded by CVID. In a prospective study of 60 adults with CVID, an allergic disease was documented in 26.6%; allergic rhinitis was the most frequent reported condition (56.2%), followed by bronchial asthma (12.5%). Serum IgE and IgA were specifically evaluated as potential biomarkers, but the abstract does not establish a universal IgE-based diagnostic threshold or a definitive predictive role for either analyte. ^[257] Consequently, total IgE, allergen-specific IgE, and skin testing should be interpreted in the context of symptoms, exposure history, and the patient’s broader immunoglobulin phenotype; a low or undetectable IgE result should not by itself invalidate a convincing clinical history. ^[257]

Core immune-function workup

Initial laboratory assessment should characterize the humoral defect with serum IgG, IgA, and IgM and should separate CVID from isolated IgG or combined IgG/IgM deficiency. The comparative cohort found clinically and immunologically meaningful differences among these groups, supporting measurement of all major immunoglobulin classes rather than reliance on IgG alone. ^[249] Results should be interpreted alongside infection pattern, gastrointestinal disease, splenomegaly, autoimmune cytopenias, and mucocutaneous viral disease, because these features help identify CVID-associated immune dysregulation and alternative CVID-like disorders. ^[249]

Flow-cytometric immunophenotyping is an important component of evaluation. Standardized multiparameter flow cytometry has been used to screen for lymphoid primary immunodeficiencies, and the PIDgeon pipeline was developed to classify immune profiles and suggest PID subtypes using flow-cytometric data, age, and immunoglobulin levels. Its development dataset included 74 healthy controls and 399 patients, including 281 lymphoid-PID and 118 non-PID individuals, and used EuroFlow-standardized data. ^[240] Automated interpretation may improve reproducibility and reporting, but it complements rather than replaces clinical review and laboratory expertise. ^[240]

Functional cellular testing may be required when the phenotype is not confined to antibody deficiency. In predominantly antibody-deficient IEI, antigen-specific CD4+ T-cell responses to SARS-CoV-2 vaccination and CMV peptides have been measured by stimulation-index analysis of effector-memory CD4+ T cells, demonstrating a framework for assessing cellular immune responsiveness in addition to serum antibodies. ^[235]^B2c Interpretation should account for CMV latency, which was specifically investigated as a modifier of T-cell responses in this population. ^[235]^B2c

Infection-directed testing

The infection history should determine targeted microbiologic and immune evaluation. For gastrointestinal symptoms or persistent diarrhea, prospective stool screening in immunoglobulin-treated hypogammaglobulinemic patients used culture, PCR, and fecal calprotectin; the cohort included 32 patients with primary CVID and demonstrated the feasibility of systematic Campylobacter investigation during Ig replacement therapy. ^[250]^C Tuberculosis assessment in IEI included exposure and symptom history, tuberculin skin testing, and chest imaging with radiography and, where available, computed tomography. If the initial TST measured 0–4 mm, it was repeated after 1–4 weeks. ^[248]^C

Immune dysregulation, organ involvement, and genetics

The immune-function workup should actively search for autoimmune and inflammatory complications. Autoimmune thrombocytopenia is frequent in CVID, and a prospective cohort defined clinically important episodes as a platelet count <50,000/µL with bleeding or <20,000/µL with or without bleeding. ^[234]^B2b Splenic ultrasound is commonly used in IEI surveillance, and a newly described “sponge-like” splenic microtexture has been reported in immune-dysregulation disorders, although its diagnostic significance remains investigational. ^[36]^B3b

Gastrointestinal and hepatic assessment is warranted because up to one-third of patients with CVID may develop GI or hepatic manifestations; CVID-associated enteropathy and liver involvement were defined using objective clinical, endoscopic, histologic, radiologic, or hemodynamic findings. ^[102]^B3b Non-invasive hepatic assessment has also been studied using the Enhanced Liver Fibrosis score and shear-wave elastography in CVID and agammaglobulinemia, but validation in these disorders remains limited. ^[136]^C4

Genetic testing is considered standard of care for newly diagnosed CVID patients in the cited practice-based report, and testing should also be reconsidered in longstanding or atypical cases. A patient diagnosed with CVID more than a decade earlier was subsequently found to have a STAT3 gain-of-function variant after unusual infections prompted reassessment. ^[44]^C4 Relevant CVID-like disorders include NFKB1 haploinsufficiency, which showed only 52% clinical penetrance in one Japanese series, and CTLA4 haploinsufficiency or LRBA deficiency, which may combine hypogammaglobulinemia with autoimmunity, inflammation, lymphoproliferation, or severe infection. ^[246]^D ^[38]^C4 ^[120]^C4 Expanded testing is therefore particularly appropriate when immune dysregulation, unusual infections, organ disease, family history, or atypical immunophenotyping is present. ^[44]^C4 ^[246]^D ^[38]^C4 ^[120]^C4

Patient-centred diagnostic practice

Because IEI diagnostics and management impose substantial physical, psychological, and socioeconomic burdens, assessment should incorporate health-related quality of life and shared decision-making. Recommended instruments include SF-36, Pediatric Quality of Life Inventory, and Patient-Reported Outcome Measurement Information System tools, selected according to age and clinical context. ^[258]^D

Reference-supported components of the CVID immunodiagnostic workup

Domain	Evaluation supported by the cited evidence
Humoral immunity	Serum IgG, IgA, and IgM; classification against isolated IgG and combined IgG/IgM deficiency; functional antibody assessment. ^[249]
Allergy and mimics	Reaction history, exposure and timing review, targeted skin or serum allergen testing, and consideration of hereditary angioedema and nonallergic mimics. ^[54]^C4 ^[257]
Cellular immunity	Multiparameter lymphocyte flow cytometry; antigen-specific CD4+ T-cell response testing when indicated. ^[240] ^[235]^B2c
Infection screening	Exposure and symptom assessment, TST with repeat testing for an initial 0–4 mm result, chest radiography and/or CT, and targeted stool testing including culture and PCR. ^[248]^C ^[250]^C
Immune dysregulation and organ disease	Assessment for autoimmune cytopenias, splenic abnormalities, enteropathy, liver involvement, and hepatic fibrosis. ^[234]^B2b ^[36]^B3b ^[102]^B3b ^[136]^C4
Etiologic diagnosis	Genetic testing for monogenic IEI, especially in atypical or dysregulated CVID-like phenotypes. ^[44]^C4 ^[246]^D ^[38]^C4 ^[120]^C4

Severity, Grading & Risk Stratification

▸CVID severity is multidimensional; infection burden, pulmonary disease, immune dysregulation, organ involvement, vaccine response, and trajectory should be assessed together. [29][148][261][265]
▸In one 150-patient cohort, 66.6% had a severe phenotype, 84.2% had recurrent respiratory infections, 45% had gastrointestinal complications, and 21% had autoimmune manifestations. [29]
▸Suspected GLILD is a high-risk pulmonary presentation requiring structured multidisciplinary evaluation; no universally accepted diagnostic or management guideline had previously existed. [147]
▸High-dose corticosteroid treatment in the cited GLILD study was defined as ≥0.3 mg/kg prednisone equivalent. [139]
▸Only 68.3% of CVID patients seroconverted after BNT162b2 vaccination, with median antibody titres 83-fold lower than in healthy controls. [142]
▸Reduced CD21low B cells, lymphopenia, reduced Treg/Th17/NK cells, soluble BCMA, and switched-memory B-cell abnormalities are potential markers but are not validated stand-alone severity grades. [142][264][265][266]
▸Prolonged or recurrent SARS-CoV-2 infection, pulmonary complications, liver disease, gastrointestinal disease, autoimmune lymphoproliferation, and malignancy-associated complications should trigger intensified longitudinal assessment. [29][147][148][155][236][259][261]

Dx Diagnostic Essentials: Do not assign CVID severity from serum immunoglobulin levels alone. Combine longitudinal infection history, pulmonary evaluation, immune phenotype, vaccine responsiveness, autoimmune or lymphoproliferative disease, and organ assessment. [29][147][148][265]

! Warning: The cited biomarkers, microbiome signatures, CT findings, and organ-assessment tools are not validated as universal CVID prognostic thresholds. Findings should guide specialist evaluation rather than replace clinical judgment. [136][147][236][260][264][265]

Scope and limitations

CVID is clinically heterogeneous, and severity should not be inferred from immunoglobulin concentrations alone. A practical assessment should integrate infection burden, pulmonary structural disease, inflammatory or autoimmune complications, organ involvement, malignancy risk, vaccine responsiveness, and disease trajectory. The available studies use different populations, endpoints, and definitions; therefore, no single, validated, universally applicable CVID severity score or risk-stratification threshold can be established from these references. ^[29]^C4^[148]^B2b^[261]^C^[265]

Clinical severity domains

A severe phenotype is characterized by substantial or recurrent infection-related morbidity and/or important noninfectious complications. In a retrospective Indian cohort of 150 patients, 66.6% were classified as having a severe phenotype; recurrent respiratory tract infection occurred in 84.2%, gastrointestinal complications in 45%, and autoimmune manifestations in 21%. All patients had hypogammaglobulinemia. These findings support respiratory, gastrointestinal, and autoimmune disease as core severity domains, but the cohort’s single-center, retrospective design limits generalizability. ^[29]^C4

Pulmonary disease is a major determinant of long-term risk. Primary antibody deficiency cohorts have frequent pulmonary complications associated with substantial morbidity and mortality, and regular CT surveillance has been advised; however, predictive risk factors for pulmonary morbidity remain incompletely defined. ^[148]^B2b Oropharyngeal microbial ecosystem perturbations may provide additional risk information: in a prospective 12-month study of 72 adults with CVID and 26 controls, respiratory microbiome composition was examined in relation to clinical and immunological characteristics and the risk of acute respiratory infection. The study supports microbiome disturbance as a potential modifier of infection risk, but does not establish a validated clinical grading threshold. ^[260]

GLILD represents a high-risk pulmonary phenotype because it is a recognized cause of morbidity and mortality in CVID. The 2026 ERS clinical practice guideline was developed because there had been no accepted diagnostic or management guideline and substantial variation between centers and countries. It used multidisciplinary consensus and GRADE methodology to address screening and diagnosis, emphasizing that suspected GLILD requires structured clinical, radiological, and multidisciplinary assessment rather than severity assignment by symptoms alone. ^[147]^A1c In a study of 56 patients treated with corticosteroids, high-dose therapy was defined as ≥0.3 mg/kg prednisone equivalent; repeated HRCT or pulmonary function testing was available in 39 patients. The study evaluated radiological and physiological response but was not a universal GLILD severity score. ^[139]^C4

Immunological and functional risk markers

Impaired vaccine response identifies limited functional humoral immunity. After BNT162b2 vaccination, only 68.3% of patients with CVID seroconverted, and median antibody titres were 83-fold lower than in healthy controls. ^[142]^B2b A separate prospective primary-antibody-deficiency study evaluated clinical outcomes, safety, humoral responses, neutralizing antibodies, and T-cell responses after vaccination, reflecting the need to assess cellular as well as antibody immunity when stratifying infection risk. ^[59]^B2b

Reduced CD21^low B-cell frequency or other abnormal B-cell subsets should be interpreted as immunophenotypic risk markers rather than stand-alone severity grades. Studies of CVID-associated autoimmunity found lymphopenia and reductions in regulatory T cells, Th17 cells, and NK cells, with NK cells lowest in patients with autoimmune complications. ^[266]^C Exploratory biomarker work evaluated soluble B-cell maturation antigen, summed κ+λ light chains, switched-memory B cells, and the VISUAL score for distinguishing CVID from selective IgA deficiency, secondary immunodeficiency, and healthy controls; these tools remain exploratory and are not validated prognostic grading systems. ^[265] Serum soluble BCMA was also associated with primary antibody deficiency status, vaccine responses, and disease complications in the COV-AD study, but requires validation before routine risk classification. ^[264]

Organ-specific and complication-related risk

Noninfectious disease increases clinical complexity and may indicate a higher-risk phenotype. CVID-related liver disease includes abnormal liver tests and clinically heterogeneous hepatic involvement, but evidence remains limited and no definitive prognostic framework is established. ^[261]^C Enhanced liver fibrosis testing and shear-wave elastography have been investigated in 22 patients with CVID and 9 with agammaglobulinemia without previously documented fibrosis; these methods are promising for non-invasive assessment but are not validated CVID severity thresholds. ^[136]^C4

Autoimmune lymphoproliferation and cytopenias require consideration of alternative or genetically defined inborn errors of immunity. In a prospective pediatric cohort, lymphoproliferation and autoimmune cytopenias were used to identify autoimmune lymphoproliferative immunodeficiencies and related disorders, which may be more severe than classic autoimmune lymphoproliferative syndrome. ^[33]^B2b CTLA4 deficiency provides an example of genotype-specific severity stratification: severe intestinal disease was associated with distinct microbiome and metabolome signatures, including Veillonella and Streptococcus as discriminatory genera, although these findings cannot be directly transferred to unselected CVID. ^[236]^C

Infection-specific risk

CVID is associated with increased risk of prolonged SARS-CoV-2 infection, reinfection, and adverse outcomes. In a multicenter European cohort of 773 patients, outcomes were assessed across vaccination, monoclonal-antibody, and antiviral eras, highlighting treatment-era effects on observed severity. ^[259] A Danish nationwide cohort found increased risks of first SARS-CoV-2 infection and reinfection compared with matched controls despite earlier vaccination of CVID patients; interpretation of severe outcomes must therefore account for vaccination timing and evolving variants. ^[155]^B2b Tuberculosis risk assessment in patients with inborn errors of immunity should combine exposure history, symptoms, tuberculin testing, repeat testing when initially negative or minimally reactive, and chest imaging; the cited cohort supports a structured strategy but does not define a CVID-specific severity grade. ^[248]^C

Practical stratification

Patients should be considered higher risk when they have progressive or recurrent lower-respiratory disease, bronchiectasis or suspected GLILD, persistent or severe infections despite immunoglobulin replacement, poor vaccine responses, marked immune-cell abnormalities, autoimmune cytopenias or lymphoproliferation, liver disease, gastrointestinal disease, or prolonged/recurrent viral infection. These features are risk indicators, not independently validated cut-offs, and should be reassessed longitudinally. ^[29]^C4^[59]^B2b^[142]^B2b^[147]^A1c^[148]^B2b^[155]^B2b^[259]^[260]^[261]^C^[266]^C

Immunoglobulin replacement remains foundational treatment for primary antibody deficiency, while subcutaneous immunoglobulin has been evaluated as a replacement and immunomodulatory treatment in CVID and autoimmune myositis. ^[156]^C4 Evidence that immunoglobulin replacement improves rhinosinusitis outcomes supports monitoring infection frequency and sinonasal disease over time, but does not by itself define systemic CVID severity. ^[263]^C Complete 22q11.2 deletion syndrome demonstrates that profound immunodeficiency can produce near-absence of gastrointestinal plasma cells, but this is a distinct disorder and should not be used as a CVID grading system. ^[262]

Suggested multidomain risk assessment

Domain	Higher-risk indicators	Evidence
Infection	Recurrent lower-respiratory infection, prolonged or recurrent viral infection, poor vaccine response	^[29]^C4^[59]^B2b^[142]^B2b^[155]^B2b^[259]
Lung	Progressive pulmonary disease, structural lung damage, suspected GLILD, abnormal serial HRCT or PFT	^[139]^C4^[147]^A1c^[148]^B2b
Immune dysregulation	Autoimmune cytopenias, lymphoproliferation, lymphopenia, reduced Treg/Th17/NK cells	^[33]^B2b^[266]^C
Gastrointestinal disease	Significant intestinal complications or severe genotype-associated enteropathy	^[29]^C4^[236]^C
Liver	Abnormal liver tests, suspected fibrosis, increased liver stiffness or ELF abnormalities	^[136]^C4^[261]^C
Biomarkers	Abnormal CD21low or switched-memory B cells, low sBCMA, altered κ+λ light chains	^[142]^B2b^[264]^[265]

Acute Management & Anaphylaxis Pathway

▸The supplied references do not provide a CVID-specific anaphylaxis algorithm, epinephrine dose, infusion-reaction grading system, or observation period; use the institutional emergency anaphylaxis protocol. [247][270]
▸SARS-CoV-2 infection in IEI warrants early risk assessment; hospitalization occurred in 20.17% of the Italian cohort, with older age and chronic lung disease associated with worse outcomes. [194]
▸COVID-19 vaccine responses in CVID are heterogeneous: cellular responses may persist or strengthen despite reduced or inconsistent antibody responses. [65][67][173][193][235][241][267][268][271][272][273]
▸A standardized SCIg reduction of 15 mg/kg/week was studied only in clinically stable adults with IgG troughs of at least 700 mg/dL, or 900 mg/dL in specified circumstances, and no significant infection for 6 months. [247]
▸Unexpected thrombocytopenia, anemia, neurologic findings, renal injury, fever, or bleeding should trigger urgent evaluation for immune-mediated thrombotic microangiopathy, including iTTP. [175]

! Warning: Do not infer that a satisfactory IgG trough or a vaccine response eliminates the risk of severe infection in CVID. Vaccine-induced antibody responses are variable, and cellular immunity may not substitute for individualized clinical assessment. [65][67][173][193][267][268][273]

CP Clinical Pearl: The evidence for SCIg dose reduction applies to a selected low-infection-burden population, not to patients presenting with active infection or recent breakthrough infections. [247]

Dx Diagnostic Essentials: In CVID, acute thrombocytopenia, anemia, neurologic symptoms, renal dysfunction, fever, or bleeding should not automatically be attributed to infection; iTTP and other immune-mediated complications require urgent consideration. [175][270]

Scope and evidence boundary

The supplied evidence supports acute assessment of infection and COVID-19 risk in CVID, immunoglobulin-replacement decisions, and recognition of selected immune-mediated emergencies. It does not provide a CVID-specific anaphylaxis algorithm, epinephrine dosing protocol, infusion-reaction grading system, or validated emergency observation period. Those elements should therefore follow the institution’s general anaphylaxis protocol rather than being inferred from these studies. ^[247]^C^[270]

Immediate triage of an acutely unwell patient

Treat new respiratory, gastrointestinal, neurologic, or systemic symptoms as potentially significant because CVID has a heterogeneous clinical spectrum, with infectious complications commonly preceding recognition and substantial non-infectious immune morbidity. ^[270] Assess airway, breathing, circulation, mental status, oxygenation, temperature, and evidence of sepsis or organ dysfunction; simultaneously clarify the patient’s CVID phenotype, current IVIg or SCIg regimen, most recent dose, infection history, and concurrent immunosuppressive treatment. The cited CVID registry and infection studies support the need for broad clinical assessment but do not establish disease-specific vital-sign thresholds. ^[194]^C4^[270]

If symptoms begin during or shortly after immunoglobulin administration, stop or interrupt the infusion and assess for anaphylaxis, severe hypersensitivity, hypotension, bronchospasm, hypoxemia, or an alternative diagnosis. The references supplied do not define an Ig-specific anaphylaxis pathway or demonstrate that IVIg and SCIg have equivalent acute reaction profiles; route selection should therefore be individualized with specialist input. ^[156]^C4^[269]^C

Infection and COVID-19 pathway

Obtain clinically indicated microbiologic testing and imaging without delaying stabilization. In a multicenter Italian IEI cohort, 20.17% of patients with SARS-CoV-2 infection required hospitalization; older age and chronic lung disease were associated with worse outcomes. CVID represented 65% of the adult IEI subgroup. ^[194]^C4 These findings support a low threshold for early clinical review in older patients and those with chronic respiratory disease, but they do not provide a universal admission rule or treatment regimen. ^[194]^C4

COVID-19 vaccination should be incorporated into prevention planning, while recognizing that responses in CVID are variable. Studies reported antibody and/or T-cell responses after primary vaccination, third-dose, booster, or repeated vaccination in CVID and other IEIs, but responses were generally weaker or less consistent than in healthy controls. ^[65]^B2b^[67]^B2b^[173]^C4^[193]^B2b^[194]^C4^[267]^C^[268]^[271]^[272]^[273] A booster increased the proportion of CVID patients exceeding prespecified anti-spike and neutralizing-antibody cutoffs in one study, from 70% to 83% for anti-spike IgG and from 70% to 80% for neutralizing antibody. ^[272] Other cohorts found durable or enhanced cellular responses despite attenuated humoral immunity, including after multiple doses. ^[67]^B2b^[173]^C4^[193]^B2b^[235]^B2c^[241]^C^[268]^[271]^[273] Consequently, vaccination should not be used as evidence that an individual CVID patient is protected; clinical risk assessment remains necessary. ^[65]^B2b^[67]^B2b^[173]^C4^[193]^B2b^[235]^B2c^[241]^C^[267]^C^[268]^[271]^[272]^[273]

Immunoglobulin replacement during acute illness or shortage

Do not make an acute SCIg dose reduction solely from an isolated IgG value. The 2025 dose-reduction study enrolled adults receiving SCIg for at least 6 months who had IgG trough levels of ≥700 mg/dL, or ≥900 mg/dL under specified conditions, and no significant infection during the preceding 6 months. Its standardized reduction was 15 mg/kg/week, equivalent to 60 mg/kg/month. ^[247]^C These eligibility criteria describe a selected, clinically stable population with a low infection burden and should not be extrapolated to patients with active, recurrent, severe, or atypical infection. ^[247]^C

IVIg and SCIg are both used for replacement therapy in primary antibody deficiency; SCIg may improve treatment convenience and quality of life, while comparative immunologic observations in CVID have been reported. ^[156]^C4^[269]^C During an acute infection, review adherence, administration technique, interval from the last dose, weight-based dosing, IgG trough trend, and breakthrough-infection history with an immunology specialist. The available references do not establish a rescue IgG threshold or support empiric extra immunoglobulin for every acute infection. ^[156]^C4^[247]^C^[269]^C

Red flags for non-infectious emergencies

CVID-associated autoimmunity can produce serious acute disease. A reported pediatric patient with CVID developed immune thrombotic thrombocytopenic purpura, requiring therapeutic plasma exchange and subsequently recovering. ^[175]^C4 Unexplained thrombocytopenia, anemia, neurologic change, renal injury, fever, or bleeding should therefore prompt urgent evaluation for thrombotic microangiopathy and hematology consultation; the cited report is a case report and does not establish a routine CVID screening or treatment pathway. ^[175]^C4

Disposition and follow-up

Escalate or admit when there is airway or circulatory compromise, hypoxemia, sepsis concern, progressive organ dysfunction, severe or rapidly worsening COVID-19, significant chronic lung disease, advanced age, or inability to maintain hydration or follow-up. The cited studies support heightened vigilance in higher-risk IEI patients but do not validate a single CVID-specific disposition score. ^[194]^C4^[270] Document the suspected trigger, treatment response, immunoglobulin product and route, and plan for specialist reassessment before the next replacement dose. ^[156]^C4^[247]^C^[269]^C

Evidence-supported acute decision points

Clinical situation	Action supported by the cited evidence	Evidence limitation
Suspected anaphylaxis or severe infusion reaction	Interrupt the immunoglobulin administration and perform immediate emergency assessment; follow the local anaphylaxis protocol.	No supplied reference specifies drug dosing, reaction grading, or observation duration. ^[247]^C^[156]^C4
Acute COVID-19 or suspected SARS-CoV-2 infection	Assess promptly for age, chronic lung disease, oxygenation, and clinical deterioration; consider early escalation when risk is high.	The cohort provides hospitalization and risk associations, not a treatment or admission threshold. ^[194]^C4
Stable patient during Ig shortage	Consider dose reduction only if the study’s selection criteria are met: SCIg for at least 6 months, IgG trough ≥700 mg/dL or specified ≥900 mg/dL, and no significant infection for 6 months.	Findings should not be extrapolated to active or high-burden infection. ^[247]^C
Cytopenia plus neurologic, renal, or systemic features	Urgently evaluate for iTTP or another thrombotic microangiopathy and involve hematology.	Evidence is based on a reported CVID-associated pediatric case. ^[175]^C4

Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics

▸Individualize long-term management according to infections, pulmonary disease, autoimmunity, inflammation, lymphoproliferation, malignancy risk, and immunologic phenotype. [90][275][276]
▸Recurrent respiratory infections may persist despite adequate trough IgG, so clinical outcomes and organ damage—not trough levels alone—should guide follow-up. [274][276]
▸Consider structured evaluation and individualized treatment for refractory chronic rhinosinusitis; supervised chest physical therapy may improve long-term lung function in children with CVID. [181][183]
▸GLILD is a major cause of morbidity and mortality; systemic corticosteroids are commonly used first line at **≥0.3 mg/kg prednisone equivalent**, with response assessed by HRCT and pulmonary-function testing. [139]
▸Rituximab-based regimens, including rituximab plus azathioprine, are specialist options for selected GLILD or lymphoid interstitial pneumonia, particularly when steroid-sparing treatment is needed. [141][187]
▸MV130 trained-immunity-based vaccination remains investigational, based on a small observational study of **10** CVID patients with recurrent respiratory infections. [274]
▸Biologics such as omalizumab and cancer immunotherapies require indication-specific specialist assessment because evidence in CVID is limited and infection risks may be substantial. [185][188]

CP Clinical Pearl: A patient’s infection burden, pulmonary trajectory, and inflammatory complications should be followed alongside immunoglobulin levels; an adequate trough IgG does not guarantee freedom from recurrent respiratory infection. [274][276]

! Warning: Rituximab, azathioprine, corticosteroids, and other biologics may further increase infectious risk in CVID. The cited evidence supports use only for selected complications under specialist supervision, not routine immunosuppression for uncomplicated antibody deficiency. [139][141][187][189][277]

Management principles

CVID is a heterogeneous primary antibody-deficiency disorder characterized by reduced immunoglobulin concentrations and impaired specific-antibody production. Long-term management must therefore be individualized according to infection burden, pulmonary disease, autoimmunity, inflammatory complications, lymphoproliferation, malignancy risk, and the patient’s immunologic phenotype. ^[90]^D5^[276]^D CVID is associated not only with recurrent acute and chronic infections but also with inflammatory and autoimmune disease, cytopenias, lymphoma, and other malignancies; these complications substantially influence long-term surveillance and treatment selection. ^[90]^D5^[275]^D^[276]^D

Infection avoidance and respiratory care

Avoidance of avoidable infectious exposures and early assessment of respiratory deterioration are central to care because CVID may cause persistent or recurrent respiratory tract infections despite apparently adequate immunoglobulin trough levels. ^[274]^[276]^D Patients with chronic or recurrent sinusitis should be evaluated for primary immunodeficiency when disease is refractory to standard therapy; systematic-review evidence supports a structured work-up and individualized medical and surgical management of chronic rhinosinusitis in primary immunodeficiency. ^[181]^B2a Fungal infection is possible in CVID, although invasive fungal infections are reported less often in predominantly humoral deficiencies than in phagocytic or cellular immune defects. ^[189]^D5^[277]^D Antifungal treatment or prophylaxis should therefore be guided by documented infection, organism, anatomic site, and the patient’s broader immune defect rather than applied routinely on the basis of CVID alone. ^[189]^D5^[277]^D

For chronic pulmonary disease, supervised airway-clearance therapy may be useful. In a randomized study including 12 children with CVID, a one-month hospital-supervised chest-physical-therapy program produced lower thoracic gas volume at one month and higher forced expiratory volume in one second at one year than unsupervised home therapy. ^[183]^A1b This evidence supports teaching and periodically reassessing airway-clearance techniques, particularly in patients with chronic sputum production, bronchiectasis, or impaired lung function. ^[183]^A1b

Immunoglobulin replacement and vaccination-based approaches

Immunoglobulin replacement is a foundational long-term treatment for clinically significant antibody deficiency, but the available references emphasize that infection control cannot be judged solely by trough IgG: recurrent respiratory infections may persist despite adequate trough levels. ^[274]^[276]^D Dosing and follow-up should consequently be guided by infection frequency, organ damage, tolerability, and functional clinical response, with regular reassessment of pulmonary and inflammatory complications. ^[276]^D

Vaccination strategies require specialist interpretation because impaired antibody production is intrinsic to CVID. A small observational proof-of-concept study evaluated MV130, a polybacterial trained-immunity-based vaccine, in 10 CVID patients with recurrent respiratory tract infections; treatment was administered for 3 months with follow-up extending to 12 months. ^[274] The study was not a definitive efficacy trial, so trained-immunity-based vaccination should be regarded as investigational rather than established replacement for immunoglobulin therapy or standard infection-prevention measures. ^[274]

GLILD and other inflammatory lung disease

Granulomatous and lymphocytic interstitial lung disease (GLILD) is a major cause of morbidity and mortality in CVID. ^[139]^C4 In the largest cited corticosteroid analysis, patients receiving high-dose systemic corticosteroids were defined by a prednisone-equivalent dose of ≥0.3 mg/kg; treatment response was assessed using serial high-resolution computed tomography and pulmonary-function testing. ^[139]^C4 The study specifically evaluated patients who had received corticosteroids without other immunosuppressive therapy at the time, supporting systemic corticosteroids as a commonly used first-line approach while recognizing that the evidence base is observational rather than definitive. ^[139]^C4

For steroid-refractory disease, relapse, or a steroid-sparing strategy, rituximab-based treatment may be considered by an experienced immunology–pulmonology team. A retrospective CVID series evaluated combined rituximab and azathioprine, with pulmonary-function tests and high-resolution CT performed before therapy and more than 6 months afterward, to determine whether pulmonary function and radiographic abnormalities improved. ^[141]^C4 A separate CVID-associated lymphoid interstitial pneumonia case reported temporary remission, reduced paraprotein and β2-microglobulin, reduced PET metabolic activity, and improved forced vital capacity after low-dose rituximab; relapse occurred after approximately 6 months, and subsequent standard-dose treatment did not provide durable remission. ^[187]^C4 These reports support rituximab, with or without azathioprine, as specialist-directed therapy for selected lymphoproliferative lung disease—not as routine treatment for uncomplicated CVID. ^[141]^C4^[187]^C4

Biologics, autoimmunity, and safety

Biologic therapy should be selected for a clearly defined indication and balanced against infection risk, impaired vaccine responses, and the possibility of worsening humoral immunodeficiency. Omalizumab successfully treated refractory chronic spontaneous urticaria in an adolescent with CVID who was already receiving immunoglobulin replacement, but this is case-report evidence and does not establish routine use in CVID. ^[185]^C4

CVID can coexist with systemic autoimmunity, including cytopenias and disorders clinically resembling Sjögren syndrome; the increased incidence of lymphoma and mucosa-associated lymphoid-tissue lymphoma further supports careful diagnostic confirmation before immunosuppression. ^[90]^D5^[275]^D Genetic and therapy-oriented classification is particularly relevant when chronic lymphoproliferation or autoimmune cytopenia suggests an ALPS-like or other autoimmune lymphoproliferative immunodeficiency rather than classic CVID. ^[7]^D5

Cancer immunotherapy requires individualized risk–benefit assessment. A case report described activity of a PD-1 inhibitor in lung adenocarcinoma with profound B-cell deficiency, but this isolated observation cannot establish safety or efficacy for CVID. ^[188]^C4 CAR-T-cell therapy and anti-CD38 monoclonal antibodies can produce distinctive gastrointestinal histologic changes in treated patients; the cited 2026 series concerned multiple myeloma and is not evidence for CVID treatment. ^[237]^C Severe SARS-CoV-2 disease has also been reported in an individual with an NF-κB2 loss-of-function variant, illustrating that genetically defined antibody-deficiency phenotypes may carry distinct viral risks. ^[144]^C4 Finally, rare CVID-like evolution has been described in patients with IgA/IgG2 deficiency and systemic lupus erythematosus after corticosteroid treatment, emphasizing the need to reassess the diagnosis when the clinical phenotype changes. ^[186]^C4

Long-term interventions supported by the cited evidence

Clinical domain	Intervention or consideration	Evidence and limitations
Antibody deficiency	Immunoglobulin replacement with clinical monitoring	Foundational treatment; recurrent infections may persist despite adequate trough IgG. ^[274]^[276]^D
Chronic rhinosinusitis	Immunodeficiency work-up; individualized medical and surgical care	Supported by systematic-review evidence in primary immunodeficiency. ^[181]^B2a
Chronic pulmonary disease	Supervised chest physical therapy and airway clearance	Randomized pediatric study showed improved selected lung-function outcomes at one year. ^[183]^A1b
GLILD	High-dose systemic corticosteroids	Studied at ≥0.3 mg/kg prednisone equivalent; HRCT and PFT response assessed. ^[139]^C4
Steroid-refractory or lymphoproliferative lung disease	Rituximab with or without azathioprine	Retrospective series and case evidence; durability and optimal regimen remain uncertain. ^[141]^C4^[187]^C4
Recurrent respiratory infections	MV130 trained-immunity-based vaccine	Small observational proof-of-concept study; investigational. ^[274]
CVID-associated urticaria	Omalizumab	Successful individual case report; insufficient evidence for routine use. ^[185]^C4

Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution

▸IVIg and SCIg are established IgRT routes in CVID; SCIg is associated with fewer systemic adverse events and greater autonomy, but regional practice remains variable. [254]
▸Monitor renal function and cardiovascular-metabolic risk during IgRT; CKD occurred in 6.27% of adults in a multicenter CVID cohort and was associated with predominantly IVIg treatment. [94]
▸Repeat TST after 1–4 weeks when the initial result is 0–4 mm as part of risk-based TB screening in IEI. [248]
▸Cryptosporidiosis occurred in 0.41% of the French IEI registry and was concentrated in combined immunodeficiency, including hyper-IgM syndromes. [101]
▸IgRT does not prevent all immune dysregulation; AITP episodes occurred in 25.5% of adults followed in a CVID cohort with AITP. [234]
▸Consider cellular immune responses when assessing vaccination in predominantly antibody-deficient IEI, because vaccine-induced T-cell responses may provide information beyond antibody titres. [235]
▸Reassess the molecular diagnosis when CVID is accompanied by atypical infection, autoimmunity, inflammation, lymphoproliferation, or malignancy. [44][107][38][120]

Dx Diagnostic Essentials: A minimally reactive TST of 0–4 mm should be repeated after 1–4 weeks in the evaluated IEI screening strategy; interpretation must remain risk- and exposure-based. [248]

! Warning: The supplied evidence does not establish a universal IgRT dose, trough target, antimicrobial-prophylaxis regimen, vaccine schedule, or transplantation indication. [94][101][234][235][248][254]

CP Clinical Pearl: Persistent inflammation, nephrotic syndrome, or progressive immune dysregulation should prompt evaluation for complications such as AA amyloidosis and for an underlying monogenic disorder. [119][44][107][38][120]

Immunoglobulin replacement

Immunoglobulin replacement therapy (IgRT) remains the cornerstone of infection prevention in CVID and may be administered intravenously (IVIg) or subcutaneously (SCIg). Available real-world evidence describes broadly comparable efficacy between routes, while SCIg is associated with fewer systemic adverse events and greater patient autonomy. Despite these advantages, IVIg remains widely used in some regions, particularly the Mediterranean area. ^[254] Route selection should therefore be individualized according to clinical response, comorbidity, venous access, treatment burden, patient preference, and local availability; the supplied studies do not establish a universal dose, target trough concentration, or switching algorithm. ^[254]

In a nationwide Spanish multicenter study, local adverse reactions (LARs) to SCIg were specifically evaluated as a potential barrier to adherence and clinician uptake. The study examined clinical, anatomical, psychosocial, and geographical predictors in patients aged ≥14 years, supporting anticipatory counseling and individualized administration planning rather than routine discontinuation for mild local reactions. ^[251] Renal monitoring is important when selecting and administering IgRT: among 367 adults with CVID, chronic kidney disease (CKD) was identified in 23 patients (6.27%) and was associated with older age, hypertension, diabetes, dyslipidemia, abnormal renal ultrasonography, and predominantly IVIg treatment. ^[94]^B2b These findings support periodic assessment of renal function, blood pressure, metabolic risk, and urinary or imaging abnormalities, particularly in patients receiving IVIg. ^[94]^B2b

IgRT does not eliminate immune dysregulation. Autoimmune thrombocytopenia (AITP) is frequent in CVID, and high-dose IVIg has conventionally been used as initial treatment for acute AITP. In a prospective observational study of 47 adults with CVID and AITP, 12 (25.5%) experienced AITP episodes during 64 months of follow-up; episodes were defined as a platelet count <50,000/µL with bleeding or <20,000/µL with or without bleeding. The study compared patients receiving SCIG (27; 57%) with those receiving IVIg (20; 43%); the supplied evidence does not provide sufficient outcome detail to conclude that either maintenance route prevents AITP more effectively. ^[234]^B2b

Infection prophylaxis and surveillance

Prophylaxis should be risk-based and integrated with exposure history, symptom review, microbiological assessment, and imaging. A single-center cohort of 117 adults with inborn errors of immunity (IEI) evaluated tuberculosis (TB) using exposure history, symptom assessment, tuberculin skin testing (TST), repeat TST after 1–4 weeks when the initial induration was 0–4 mm, and chest radiography or computed tomography when available. Patients underwent standard clinical assessment followed by appropriate treatment and follow-up. ^[248]^C These data support repeat testing after a minimally reactive initial TST and use of chest imaging when clinical or epidemiological risk warrants it, while recognizing that the supplied abstract does not report diagnostic yield or comparative test performance. ^[248]^C

Cryptosporidiosis is an important opportunistic infection in IEI. In the French CEREDIH registry, 149 of 10,004 patients had at least one proven parasitic infection (approximately 1.4%); 41 patients had cryptosporidiosis, representing 27.5% of parasitic-infection cases and 0.41% of the total registry. Combined immunodeficiency accounted for 25 cases, including eight hyper-IgM syndromes. ^[101]^B3b Prevention should consequently emphasize exposure-risk assessment, prompt investigation of persistent or unexplained diarrhoea, and specialist management of proven infection; the supplied study does not establish a specific antimicrobial prophylaxis regimen. ^[101]^B3b

Immune reconstitution and immune-dysregulation monitoring

The supplied evidence does not demonstrate that IgRT restores defective endogenous antibody production. Immune assessment should therefore remain phenotype-directed. After two doses of mRNA COVID-19 vaccine, antigen-specific CD4+ T-cell responses were assessed in 114 IEI patients, predominantly with predominantly antibody-deficient disease, and 38 healthy controls; responses were evaluated using effector-memory CD4+ T-cell assays, with CMV latency also examined. ^[235]^B2c Vaccination decisions should therefore not rely solely on antibody titres in antibody-deficient patients, and cellular responses may be relevant, although the abstract does not provide a universal correlate of protection or a revised vaccine schedule. ^[235]^B2c

CVID management also requires surveillance beyond infection prevention. Autoimmune or autoinflammatory manifestations occurred in 26.3% of 825 Algerian patients with IEI, with autoimmune features in 19.8%; nearly half of these manifestations were present at initial IEI presentation. ^[238] In Moroccan children with IEI, autoimmune manifestations were also systematically recorded in a national registry, reinforcing the need for age-appropriate monitoring. ^[252] Malignancy occurred in 40 of 355 adults with IEI in a Turkish single-center cohort, supporting individualized malignancy surveillance. ^[97]^C4 Persistent inflammation and infection may cause AA amyloidosis, illustrated by a CVID case with recurrent pneumonia, sinusitis, osteomyelitis, sepsis, and subsequent nephrotic syndrome due to biopsy-confirmed AA amyloidosis. ^[119]^C4

Genetic reassessment is clinically relevant when infections, autoimmunity, lymphoproliferation, or inflammation are atypical. NFKB1-related disease may combine hypogammaglobulinemia with fever, autoimmunity, autoinflammation, and malignancy, while CTLA4 haploinsufficiency and LRBA deficiency can produce severe infections, autoimmune cytopenias, inflammation, and lymphoproliferation. ^[107]^C4^[38]^C4^[120]^C4 A longstanding CVID diagnosis was subsequently revised to STAT3 gain-of-function disease after genetic testing prompted by unusual nontuberculous infection and lymphadenitis, enabling directed therapy. ^[44]^C4 Genetic testing should therefore be considered in newly diagnosed CVID and revisited when the phenotype evolves. ^[44]^C4

Practical limits of the evidence

The supplied studies are predominantly observational cohorts, registries, or case reports. They inform route selection, safety surveillance, infection screening, and recognition of immune dysregulation, but do not define universal IgRT dosing, antimicrobial-prophylaxis protocols, vaccine schedules, or criteria for hematopoietic transplantation. ^[94]^B2b^[101]^B3b^[234]^B2b^[235]^B2c^[248]^C^[254]

Evidence-informed management priorities

Domain	Evidence-informed action	Supporting evidence
IgRT route	Individualize IVIg versus SCIg; counsel about local reactions and autonomy	^[251]^[254]
Renal safety	Monitor renal function, blood pressure, metabolic risk, and urinary/imaging abnormalities	^[94]^B2b
TB screening	Review exposure and symptoms; repeat TST after 1–4 weeks if 0–4 mm; add chest imaging when indicated	^[248]^C
Enteric infection	Investigate persistent diarrhoea promptly and assess Cryptosporidium exposure risk	^[101]^B3b
Immune dysregulation	Monitor cytopenias, autoimmunity, inflammation, lymphoproliferation, and malignancy	^[97]^C4^[119]^C4^[238]^[252]
Diagnostic refinement	Pursue or revisit genetic testing when the phenotype is atypical or progressive	^[44]^C4^[107]^C4^[38]^C4^[120]^C4

Complications, Comorbidities & Iatrogenic Risks

▸CVID complications extend beyond infection and include gastrointestinal disease, autoimmunity, autoinflammation, lymphoproliferation, malignancy, bronchiectasis, hepatopathy, and premature mortality. [16,19,29,278]
▸In an Indian CVID cohort, gastrointestinal complications occurred in 45% and autoimmune manifestations in 21%; recurrent respiratory infections occurred in 84.2%. [29]
▸In the French IEI registry, cryptosporidiosis occurred in 0.41% of the total cohort and represented 27.5% of patients with documented parasitic infection. [101]
▸Autoimmune and/or autoinflammatory disease occurred in 26.3% of 825 Algerian patients with IEI, although these data were not limited to CVID. [238]
▸Hepatic manifestations in hospitalized adults with CVID were associated with mortality and worse hospital outcomes. [19]
▸Complicated CVID is associated with higher mortality than infection-only CVID. [16]
▸SCIg may offer fewer systemic adverse reactions and greater autonomy than intravenous therapy, but local reactions can impair adherence and confidence in treatment. [251,279]

! Warning: Complication frequencies from IEI cohorts cannot automatically be treated as CVID-specific estimates because several studies included multiple primary immunodeficiency diagnoses. [101,108,238,244]

CP Clinical Pearl: The presence of autoimmune, inflammatory, lymphoproliferative, hepatic, or bronchiectatic disease identifies a clinically complicated phenotype that warrants longitudinal multisystem surveillance. [16,19,238,253,278]

Dx Diagnostic Essentials: Cytokine testing may assist recognition of autoimmune/inflammatory CVID in resource-limited settings, but the supplied evidence does not validate it as a replacement for standard immunophenotyping and flow-cytometric assessment. [244]

Overview

Common variable immunodeficiency (CVID) is associated with both infection-related morbidity and non-infectious immune-dysregulation complications, including enteropathy, lymphoproliferation, malignancy, autoimmune disease, inflammatory disease, hepatopathy, and premature mortality. ^[278]^C The clinical phenotype is heterogeneous: in an Indian cohort of 150 patients, 84.2% had recurrent respiratory tract infections, 45% had gastrointestinal complications, and 21% had autoimmune manifestations. ^[29]^C4 In a Moroccan multicenter cohort, clinical, immunological, and genetic features were assessed across 61 patients, underscoring the need to interpret complication rates in relation to ancestry, referral setting, diagnostic criteria, and cohort composition. ^[255]

Infectious complications

Gastrointestinal infection remains an important complication of antibody deficiency despite immunoglobulin replacement. A prospective Bordeaux study enrolled 73 immunoglobulin-treated patients with hypogammaglobulinemia, including 32 with CVID, and screened stool samples for Campylobacter using culture and polymerase-chain-reaction testing; faecal calprotectin and immune profiles were also assessed. ^[250]^C The study specifically addressed the predisposition of hypogammaglobulinemic patients to gastrointestinal Campylobacter infection and included repeat sampling after 6–12 months in 38 participants. ^[250]^C

Cryptosporidiosis is an opportunistic parasitic infection reported in patients with inborn errors of immunity (IEI). In the French CEREDIH registry, 149 of 10,004 patients (approximately 1.4%) had at least one proven parasitic infection, while 41 patients (27.5% of those with parasitic infection; 0.41% of the entire registry) had cryptosporidiosis. ^[101]^B3b Combined immunodeficiency accounted for 25 of the cryptosporidiosis cases, including 8 patients with hyper-IgM syndromes; these data concern IEI overall and should not be extrapolated directly to CVID. ^[101]^B3b

Autoimmunity, autoinflammation, and immune dysregulation

Autoimmune and inflammatory disease is a major component of complicated CVID. In an adult CVID cohort of 81 patients followed for a mean of 8.5 years, investigators assessed monoautoimmunity, overt polyautoimmunity, and latent polyautoimmunity, defined as autoantibodies without clinically evident autoimmune disease. ^[278]^C The study characterized polyautoimmunity as a manifestation of broader immune dysregulation occurring alongside complications such as enteropathy, lymphoproliferation, and malignancy. ^[278]^C

In a broader Algerian IEI cohort of 825 patients, autoimmune and/or autoinflammatory manifestations occurred in 217 patients (26.3%) and were the initial clinical presentation in nearly half of affected patients. ^[238] Autoimmune features were documented in 163 patients (19.8%), including 26 patients (3.2% of the total cohort) with concurrent autoinflammatory findings. ^[238] These findings support active assessment for immune dysregulation even when infection is the presenting concern, while recognizing that the cohort included multiple IEI diagnoses rather than CVID alone. ^[238]

CVID patients with autoimmune and inflammatory complications demonstrate molecular abnormalities in T cells and monocytes. An exploratory transcriptomic and proteomic study reported broader cellular and molecular changes in patients with complicated CVID than in healthy controls and evaluated inflammatory mediators including IL-1β, IL-18, CXCL9, and CXCL10. ^[83]^B3b Tryptophan–kynurenine metabolites and neopterin were also investigated in CVID in relation to inflammation, immunologic phenotype, and gut microbial dysbiosis. ^[9]^C4 Serum cytokine testing was evaluated as a potential alternative or adjunct to lymphocyte-subset flow cytometry for identifying autoimmune/inflammatory disease in resource-limited settings; the study did not establish cytokine testing as a replacement standard. ^[244]

Pulmonary and hepatic comorbidity

Bronchiectasis is a prominent chronic respiratory complication. In the New Zealand CVID study, which enrolled 108 patients representing approximately 70% of known CVID patients in the country, Māori patients had a high prevalence of bronchiectasis and complete IgA deficiency. ^[253]^C The finding indicates an important ethnic-specific burden but does not provide a universal prevalence estimate for all CVID populations. ^[253]^C

Hepatic disease is clinically consequential in CVID. A nationwide United States analysis of CVID-associated adult hospitalizations evaluated the prevalence and spectrum of hepatic manifestations, associated comorbidities and risk factors, and hospital outcomes using the National Readmission Database. ^[19]^C4 Hepatic manifestations were associated with mortality and worse hospital outcomes in that analysis. ^[19]^C4 A separate CVID study examined hepatopathy and cytomegalovirus status in relation to expansion of CD57+ CD8 T cells; the study included 131 patients with a median follow-up of 9 years and investigated whether this T-cell phenotype had diagnostic value. ^[239]

Malignancy and mortality

Malignancy is an established concern across IEI and is particularly relevant when immune dysregulation or lymphoproliferation is present. In a single-center adult IEI study of 355 patients, 40 patients had neoplasia; their median age was 51.58 years with a range of 18–91 years. ^[97]^C4 The study emphasizes the need for individualized surveillance because IEI presentations and malignancy risks are heterogeneous. ^[97]^C4

Head and neck cancer (HNC) risk was evaluated using TriNetX data and Surveillance, Epidemiology, and End Results data from 2017–2021; the study compared patients with primary immunodeficiency disorders with the general population and assessed outcomes in propensity-matched HNC cohorts. ^[108]^B3b The investigation was designed to quantify HNC incidence and compare outcomes, but the supplied abstract does not provide the numerical incidence or outcome estimates. ^[108]^B3b

Premature mortality is concentrated in patients with complicated CVID. A tertiary-center study compared deceased patients with complicated CVID with matched living controls to identify clinical and laboratory indicators of premature death. ^[16]^B3b The authors specifically contrasted complicated CVID with infection-only CVID, reporting that immune-dysregulation complications are associated with higher mortality. ^[16]^B3b Low serum soluble B-cell maturation antigen was also investigated in primary and secondary antibody deficiency in relation to disease complications and SARS-CoV-2 vaccine responses, but the supplied evidence does not establish it as a validated mortality predictor. ^[264]

Iatrogenic risks and treatment-related considerations

Immunoglobulin replacement reduces infectious risk but does not eliminate gastrointestinal pathogen carriage or infection susceptibility, as illustrated by prospective Campylobacter screening in treated hypogammaglobulinemic patients. ^[250]^C Subcutaneous immunoglobulin (SCIg) is used as an alternative to intravenous immunoglobulin and is associated with fewer systemic adverse reactions and greater patient autonomy in registry data. ^[279] However, local adverse reactions are common enough to affect adherence and clinician confidence; a nationwide multicenter Spanish study investigated clinical, anatomical, psychosocial, and geographical predictors of these reactions. ^[251] Spanish registry data from 223 adults with primary or secondary immunodeficiency further assessed adverse effects, infection control, autonomy, and quality-of-life outcomes with SCIg. ^[279] Treatment selection should therefore balance infection control, patient preference, injection-site tolerability, adherence, and the need for monitoring of ongoing non-infectious complications. ^[251]^[279]

Clinical implications

CVID follow-up should not focus solely on recurrent infection: assessment should also address bronchiectasis, gastrointestinal disease, autoimmunity, autoinflammation, lymphoproliferation, liver disease, malignancy, and treatment tolerability. ^[19]^C4^[29]^C4^[97]^C4^[238]^[253]^C^[278]^C Patients with immune-dysregulation features require particularly careful longitudinal assessment because this phenotype is associated with higher mortality. ^[16]^B3b

Major complication domains and supporting evidence

Domain	Evidence relevant to CVID/IEI
Respiratory	Recurrent respiratory infections occurred in 84.2% of 150 Indian CVID patients; bronchiectasis was highly prevalent in the Māori subgroup of the New Zealand CVID cohort. ^[29]^C4^[253]^C
Gastrointestinal/infectious	Gastrointestinal complications occurred in 45% of the Indian CVID cohort; Campylobacter screening was performed in 73 treated hypogammaglobulinemic patients, including 32 with CVID. ^[29]^C4^[250]^C
Autoimmune/autoinflammatory	Autoimmune and/or autoinflammatory manifestations occurred in 26.3% of 825 Algerian IEI patients; polyautoimmunity was specifically studied in 81 adults with CVID. ^[238]^[278]^C
Hepatic	Hepatic manifestations in hospitalized adults with CVID were associated with mortality and worse hospital outcomes. ^[19]^C4
Malignancy	Neoplasia occurred in 40 of 355 adults with IEI in a single-center study; HNC incidence and outcomes were evaluated in comparative population datasets. ^[97]^C4^[108]^B3b
Treatment-related	SCIg is associated with fewer systemic reactions and greater autonomy, but local adverse reactions may affect adherence. ^[251]^[279]

Prognosis & Natural History

▸CVID prognosis is heterogeneous; immune-dysregulation complications (CVIDc) are associated with higher mortality than infection-only disease (CVIDio). [16]
▸Bronchiectasis was reported in **13.4% (197/1470)** of USIDNET-registered CVID patients. [283]
▸GLILD affects approximately **10–20%** of patients with CVID disorders and can impair exercise capacity, lung function, quality of life, and survival. [287][288]
▸Chronic enteropathy, permanent organ damage, older age, and frequent infections are associated with worse or more concerning quality-of-life outcomes. [286]
▸Cancer occurs more often in IEI than in immunocompetent populations and is an important cause of death; malignancy is a major CVID prognostic concern. [86][282]
▸CVID phenotypes and cellular immune abnormalities may evolve over time, including in association with CMV or EBV viremia. [280]

! Warning: Do not assume that immunoglobulin replacement eliminates long-term risk: immune dysregulation, bronchiectasis, GLILD, enteropathy, viral complications, organ damage, and malignancy may determine prognosis. [16][129][280][282][283]

CP Clinical Pearl: Longitudinal assessment should include complications and patient-reported outcomes, not infection frequency alone; quality of life may remain impaired because of chronic enteropathy, permanent organ damage, fatigue, or perceived health deterioration. [258][286]

Overview

Common variable immunodeficiency (CVID) has a heterogeneous, lifelong course characterized not only by recurrent or severe infection but also by immune dysregulation, organ damage, impaired quality of life, and malignancy risk. ^[16]^B3b^[86]^A1a^[282] Prognosis is therefore determined by the individual complication profile rather than by hypogammaglobulinemia alone. ^[16]^B3b^[286] Patients with an infection-only phenotype (CVIDio) generally have a more favorable prognosis than those with immune-dysregulation complications (CVIDc), who have higher mortality. ^[16]^B3b

Pulmonary disease and GLILD

Chronic respiratory disease is a major determinant of long-term morbidity. In the USIDNET registry, physician-reported bronchiectasis was present in 13.4% (197/1470) of patients with CVID; the study specifically evaluated its relationship with recurrent pulmonary infection and other respiratory comorbidities. ^[283] Bronchiectasis represents established structural lung disease and may contribute to persistent respiratory symptoms, recurrent infection, and progressive organ damage. ^[283]

Granulomatous-lymphocytic interstitial lung disease (GLILD) is a noninfectious immune-dysregulatory complication reported in approximately 10–20% of patients with CVID disorders. ^[288]^C It is clinically important because it may impair exercise capacity, pulmonary function, and health-related quality of life, and has historically been described as a potentially fatal complication. ^[287]^C^[288]^C Patients may report exertional dyspnea; prospective assessment has used the 6-minute walk test and the King's Brief Interstitial Lung Disease Questionnaire to quantify functional and quality-of-life outcomes. ^[288]^C

The 2026 ERS clinical practice guideline was developed because GLILD diagnosis and management previously varied substantially between centers and countries and lacked an accepted guideline. ^[147]^A1c The guideline uses evidence review, GRADE methodology, and multidisciplinary consensus to address screening and diagnosis in CVID. ^[147]^A1c Small retrospective series suggest that disease activity can improve with immunosuppression: in one six-patient series, first-line rituximab monotherapy was assessed using symptoms, quality of life, immune parameters, pulmonary function testing, and computed tomography. ^[287]^C However, the small sample size and observational design mean that treatment response and long-term prognosis remain uncertain. ^[287]^C

Infection-related trajectory

CVID can produce unusually prolonged or severe infections because impaired antibody responses may coexist with cellular immune abnormalities. ^[129]^B2b^[280] Campylobacter infection, which ordinarily resolves within 5–7 days in immunocompetent individuals, may be prolonged or severe in CVID and require antibiotics or more intensive treatment. ^[129]^B2b A retrospective cohort included 14 affected patients and 95 CVID controls, with a median follow-up exceeding 20 years, allowing assessment of clinical, immunologic, microbiologic, and treatment outcomes over an extended period. ^[129]^B2b

Viral complications may also influence the evolving phenotype. In a 31-patient retrospective CVID analysis, investigators evaluated cytomegalovirus and Epstein–Barr virus viremia in relation to immunophenotype, clinical outcome, and time-dependent changes in disease manifestations. ^[280] The study highlights that CVID-associated cellular immune defects and clinical phenotypes may change over time, although the available abstract does not establish a universal progression pattern. ^[280] Severe or unusual opportunistic infection should prompt reassessment of the diagnosis and immune phenotype, because Good syndrome—thymoma-associated immunodeficiency—can resemble CVID while involving combined B- and T-cell defects and may be misdiagnosed as CVID. ^[81]^C4^[212]^C4

Malignancy and immune dysregulation

Malignancy is an important adverse prognostic outcome in CVID and other inborn errors of immunity; systematic-review evidence identifies cancer as more frequent than in immunocompetent populations and as an important cause of death in IEI. ^[86]^A1a A multicenter CVID study evaluated hematologic and solid-organ malignancies and examined immune dysregulation as a possible risk factor for carcinogenesis. ^[282] The study reflects the current clinical view that autoimmune disease, lymphoproliferation, and malignancy are major noninfectious complications that increasingly influence prognosis. ^[282]

The available evidence does not support a single reliable risk score for premature death. A retrospective tertiary-center study compared patients with CVIDc who died prematurely with matched living CVIDc controls to identify clinical and laboratory indicators of excess mortality. ^[16]^B3b These findings support intensified longitudinal surveillance in CVIDc, but exploratory retrospective data should not be interpreted as establishing causality or a definitive prediction model. ^[16]^B3b

Quality of life and cumulative burden

CVID-related prognosis includes patient-reported health and functional status. In an eight-year observational study of 140 patients assessed twice yearly, more frequent infections, female sex, and chronic enteropathy were associated with worse global CVID-specific quality-of-life scores. ^[286] Permanent organ damage and older age increased the perceived risk of health deterioration, while chronic enteropathy was associated with fatigue. ^[286] These findings indicate that cumulative organ damage and gastrointestinal disease may remain clinically important even when acute infections are controlled. ^[286]

Neurologic and cognitive consequences are being investigated but remain incompletely defined. A retrospective cross-sectional study compared 35 patients with CVID with 40 age- and sex-matched healthy controls using Montreal Cognitive Assessment testing and automated segmentation of high-resolution brain MRI. ^[281] Because the study was cross-sectional and small, it cannot determine whether observed structural or cognitive differences predict future disability. ^[281] Current IEI practice increasingly emphasizes routine health-related quality-of-life assessment and shared decision-making alongside medical outcomes. ^[258]^D

Overall prognostic interpretation

The natural history of CVID is variable and may evolve from infection-predominant disease to a phenotype dominated by bronchiectasis, GLILD, enteropathy, autoimmunity, lymphoproliferation, viral complications, or malignancy. ^[16]^B3b^[129]^B2b^[280]^[282]^[283] The strongest adverse prognostic signals supported by the cited evidence are immune-dysregulation complications, permanent organ damage, chronic enteropathy, significant lung disease, and malignancy. ^[16]^B3b^[286]^[282]^[283] Prognosis should therefore be reassessed longitudinally using clinical complications, pulmonary function and exercise capacity when indicated, infection and viral history, organ-damage burden, malignancy surveillance, and patient-reported quality of life. ^[147]^A1c^[258]^D^[286]^[288]^C

Major prognostic domains in CVID

Domain	Evidence relevant to natural history
Immune dysregulation	CVIDc carries higher mortality than infection-only CVID. ^[16]^B3b
Structural lung disease	Bronchiectasis was reported in 13.4% of 1470 registry patients. ^[283]
GLILD	Reported in approximately 10–20%; associated with respiratory and quality-of-life burden. ^[287]^C^[288]^C
Infection	Campylobacter may be prolonged or severe; immunocompetent illness usually lasts 5–7 days. ^[129]^B2b
Malignancy	Cancer is more frequent in IEI than in immunocompetent populations and contributes importantly to mortality. ^[86]^A1a
Quality of life	Infections, chronic enteropathy, permanent organ damage, and older age are associated with worse perceived health or quality of life. ^[286]

Special Populations and Pregnancy

▸Pediatric CVID has high morbidity and mortality; switched memory B cells <5/mL identify highest-risk children.
▸Pregnancy in CVID is high-risk (preterm labour, preeclampsia, stillbirth) but fertility is normal; IVIG is safe and breastfeeding is protective.
▸Elderly patients present with more non-infectious features; comorbidities demand individualized immunoglobulin dosing and infection surveillance.

Dx Diagnostic Essentials: In children with recurrent sinopulmonary infections, failure to thrive, or autoimmune cytopenias, check immunoglobulin levels and switched memory B cells, CVID is often missed until irreversible lung damage occurs.

Prognosis in CVID varies by age at presentation and by the physiologic demands of pregnancy, aging, and immune compromise. These special populations require tailored diagnostic thresholds and modified strategies.

Pediatrics

In children, recurrent sinopulmonary infections are the most common presentation, but failure to thrive, autoimmune cytopenias, bronchiectasis, and growth hormone deficiency are seen ^[21]^C4. Diagnostic delay averages 8.9 years from symptom onset, and the clinical signature, frequency of common infections and antibiotic prescriptions, can be detected by machine learning up to 10 years before formal diagnosis ^[215]^B3b^[223]^B2b. Patients with <5 switched memory B cells/mL (Group I) are at higher risk for meningitis, sepsis, bronchiectasis, granulomatous lung disease, autoimmune cytopenias, and hematologic malignancies ^[77]^B2b. Severe fatigue affects nearly 20% of pediatric patients and is not related to disease activity ^[219]^B2c. Subcutaneous immunoglobulin (SCIG) is well tolerated even in children with comorbid bleeding disorders, enabling home therapy ^[159]^C4. Mortality is increased in pediatric-onset CVID, with death most often from infection, and lung disease (OR 5) and severe/opportunistic infection (OR 9) directly associated with mortality ^[171]^B2b. Early diagnosis and regular surveillance for noninfectious complications are paramount.

Pregnancy

Fertility in women with CVID is not decreased, but pregnancies carry significantly higher risks. In a cohort of 54 women with 115 pregnancies, complications included threat of preterm labour (p<0.0001), vaginal bleeding (p=0.0001), eclampsia/preeclampsia (p=0.009), and (p<0.0001) compared with the general population; low birth weight (<2500 g) was also more frequent (p<0.0001) ^[200]^B2b. The number of unsuccessful pregnancies was higher in symptomatic untreated women ^[200]^B2b.

Immunoglobulin replacement therapy (IgRT) should be continued throughout pregnancy. Intravenous immunoglobulin (IVIG), dosed to maintain trough IgG >500-700 mg/dL, is safe and has no moderate or severe adverse effects in pregnancy ^[200]^B2b. Cord/maternal blood ratios of total IgG and specific antibodies show good placental transfer ^[135]^C4. is encouraged: colostrum from CVID mothers contains protective antibodies that inhibit enteropathogenic E. coli adhesion, providing local protection for the infant ^[135]^C4. IgA deficiency was found in 23% of children born to CVID mothers, warranting follow-up ^[200]^B2b. A multidisciplinary team including maternal-fetal medicine, immunology, and neonatology is essential ^[137]^D5.

Elderly

CVID diagnosed after age 50 often presents with bronchitis, arthritis, depression, and fatigue rather than classic infection patterns ^[220]^B2b. Chronic lung disease, which increases with age, is a major risk factor for hospitalization (p=0.0008) ^[194]^C4. Comorbidities such as diabetes, , and renal impairment complicate management. IgG trough targets should be individualized, balancing infection prevention against volume overload risk. Subcutaneous immunoglobulin may be preferred to avoid hemodynamic stress of IVIG in frail patients. Elderly patients have higher rates of lymphoma than younger cohorts, though not always statistically significant ^[220]^B2b.

Immunocompromised Settings

Patients with CVID who require additional immunosuppression (e.g., for autoimmune complications or post-transplant) face compounded infection risk. SARS-CoV-2 infection can elicit robust T-cell responses even without antibody production in some CVID patients ^[221]^B3b. Mortality from in CVID is highest in those aged 50-60, dramatically exceeding general population rates (14.3% vs 0.6%) ^[194]^C4. Persistent vaccine-derived poliovirus infection, although rare, has been reported in CVID and may require novel antivirals such as remdesivir ^[177]^C4. Any addition of immunosuppressive therapy demands intensified surveillance and antimicrobial prophylaxis.

Pearl: Elderly patients present with more non-infectious features; comorbidities demand individualized immunoglobulin dosing and infection surveillance.

Prevention, Screening & Surveillance

▸Use individualized, phenotype-based surveillance because CVID complications vary substantially among patients. [32][232]
▸IgRT is the cornerstone of infection prevention; intravenous and subcutaneous routes have similar efficacy, while subcutaneous therapy may reduce systemic adverse events and increase autonomy. [254]
▸Monitor platelet counts and bleeding symptoms because autoimmune thrombocytopenia affected 25.5% of a prospective CVID cohort with this complication. [234]
▸Offer COVID-19 booster vaccination according to current recommendations; antibody responses may be weak, but T-cell and memory B-cell responses can persist or improve. [65][173][193][241][267][268]
▸Do not interpret antibody testing as the sole measure of vaccine benefit because cellular immunity may remain detectable in patients with poor serologic responses. [65][173][271]
▸Maintain gastric and malignancy surveillance; gastric precancerous lesions occurred in approximately one-third of patients undergoing endoscopy in a prospective CVID study. [290]
▸Apply risk-based tuberculosis screening using exposure and symptom assessment, tuberculin testing, repeat testing after 1–4 weeks for an initial 0–4 mm result, and chest imaging when indicated. [248]
▸Assess long COVID and quality of life routinely; long COVID was reported by 65.7% of patients in one Italian CVID cohort. [100][202]

HY High Yield: A weak or absent post-vaccination antibody response does not necessarily indicate absent protection in CVID: T-cell responses may remain robust, and booster vaccination can improve memory B-cell and cellular responses. [65][173][193][241][267][268]

! Warning: CVID patients remain vulnerable to prolonged SARS-CoV-2 infection, reinfection, severe disease, and long COVID despite vaccination; preventive vaccination should not replace prompt evaluation and risk-based management of suspected infection. [100][193]

Dx Diagnostic Essentials: Tuberculosis evaluation in IEI should integrate exposure history, symptoms, skin testing, and imaging; a negative or initially nonreactive test should be interpreted in the context of immune dysfunction and clinical suspicion. [248]

Preventive care framework

Common variable immunodeficiency (CVID) requires individualized, longitudinal surveillance because patients may experience recurrent infection, autoimmune cytopenias, lymphoproliferation, enteropathy, chronic respiratory disease, and malignancy; the clinical phenotype is heterogeneous, including patients without disease-related complications, autoimmune cytopenias, polyclonal lymphoproliferation, or unexplained enteropathy. ^[32]^C4 Monitoring should therefore be based on the patient’s infection history, organ involvement, immune phenotype, family history, and any identified genetic cause rather than on a single fixed schedule. ^[32]^C4^[232]^C4

Immunoglobulin replacement and infection prevention

Immunoglobulin replacement therapy (IgRT), administered intravenously or subcutaneously, remains the cornerstone of infection prevention in CVID. ^[254] Real-world data describe broadly similar efficacy between intravenous and subcutaneous treatment, while subcutaneous therapy is associated with fewer systemic adverse events and greater patient autonomy. ^[254] Choice of route should therefore incorporate clinical response, adverse effects, venous access, treatment burden, and patient preference. ^[254]

Patients should be assessed during follow-up for breakthrough infections, treatment adherence, tolerability, and complications requiring a change in IgRT strategy. Autoimmune thrombocytopenia is a frequent CVID complication; in a prospective cohort of 47 adults with CVID and autoimmune thrombocytopenia, 25.5% experienced an autoimmune thrombocytopenic episode during a median 64-month follow-up period. ^[234]^B2b Platelet surveillance should be intensified when bruising, petechiae, mucosal bleeding, or other symptoms suggest immune thrombocytopenia. ^[234]^B2b

COVID-19 vaccination and follow-up

CVID and other inborn errors of immunity (IEI) are associated with increased risk from COVID-19, making vaccination an important preventive intervention. ^[59]^B2b^[193]^B2b Responses are heterogeneous: after primary mRNA vaccination, some patients with CVID or predominantly antibody deficiency develop spike-specific antibodies, whereas others have weak or absent humoral responses; cellular responses may nevertheless be detectable. ^[59]^B2b^[65]^B2b^[173]^C4^[271]

A third mRNA vaccine dose can improve responses in CVID, although antibody responses remain impaired in a subset. ^[193]^B2b In primary antibody deficiency, booster vaccination was reported to restore or improve an attenuated IgG1 memory B-cell response. ^[268] Studies of booster vaccination in IEI also support persistence or enhancement of spike-specific antibody and T-cell responses, but the magnitude varies by diagnosis and immune defect. ^[267]^C Following multiple doses, patients with IEI may demonstrate comparatively lower humoral responses but preserved or enhanced T-cell immunity relative to healthy controls. ^[241]^C A robust T-cell response has also been observed in CVID patients who do not mount an adequate antibody response. ^[173]^C4

Antibody testing alone should not be used as the sole indicator of vaccine benefit because cellular immunity can be present despite limited seroconversion. ^[65]^B2b^[173]^C4^[271] T-cell responses may be influenced by factors such as cytomegalovirus latency, which has been specifically evaluated in predominantly antibody-deficient patients. ^[235]^B2c Vaccination should follow current circulating-strain and public-health recommendations, with specialist review of timing in patients receiving immunosuppressive therapy or experiencing acute illness; the cited studies support booster immunization but do not establish one universal CVID-specific schedule. ^[193]^B2b^[267]^C^[241]^C

Clinical protection remains incomplete. CVID cohorts have reported prolonged viral positivity, reinfections, increased hospitalization or mortality risk during infection, and a high prevalence of long COVID; in one multicenter Italian cohort, 65.7% of 175 patients reported long COVID, with fatigue the most frequent symptom at 75.7%. ^[100]^B2b Vaccination should therefore be combined with prompt clinical assessment of respiratory symptoms and early consideration of locally available COVID-19 treatment pathways for eligible high-risk patients. ^[100]^B2b

Malignancy surveillance

CVID is associated with increased risk of malignancy, particularly B-cell lymphoma and gastric cancer. ^[290]^C^[291] In a five-year prospective CVID study involving 512 patients and 400 upper gastrointestinal endoscopies, histology identified gastric precancerous lesions in approximately one-third of patients; endoscopy frequency declined during the COVID-19 period from 0.58 to 0.39 procedures per patient-year. ^[290]^C These findings support maintaining planned gastrointestinal surveillance and avoiding preventable interruptions, while tailoring endoscopy to prior findings, symptoms, and specialist assessment. ^[290]^C

Cancer risk is not limited to the stomach or lymphoid system. A retrospective adult IEI study identified neoplasia in 40 of 355 patients, underscoring the need for personalized monitoring. ^[97]^C4 Patients with primary immunodeficiency disorders may also have increased head and neck cancer risk compared with the general population, although the cited database study is observational and does not define a CVID-specific screening interval. ^[108]^B3b Routine age-appropriate population cancer screening should therefore be maintained, with additional targeted evaluation for persistent lymphadenopathy, splenomegaly, unexplained weight loss, gastrointestinal symptoms, abnormal blood counts, mucosal lesions, or other red flags. ^[97]^C4^[108]^B3b^[290]^C^[291]

Tuberculosis and infection screening

Tuberculosis screening should be risk-based and include exposure history, symptom review, and appropriate chest imaging. ^[248]^C In adults with IEI, a tuberculin skin test may be repeated after 1–4 weeks when the initial induration is 0–4 mm, with chest radiography and, when clinically indicated, computed tomography incorporated into assessment. ^[248]^C Because diagnostic performance may be affected by immune dysfunction, negative testing should not override compatible symptoms, epidemiologic exposure, or imaging abnormalities. ^[248]^C

Genetic and psychosocial surveillance

Targeted next-generation sequencing can identify monogenic causes in selected patients meeting CVID criteria, particularly when onset is before age 18 years, autoimmunity, low memory B-cell numbers, family history, or lymphoproliferation is present. ^[232]^C4 Genetic clarification can support individualized surveillance and family counseling, although a negative panel does not exclude CVID or other IEI. ^[232]^C4

Health-related quality of life should be assessed periodically because predominantly antibody-deficient patients experience substantial physical, psychological, and social burden related to infections and noninfectious complications. ^[202]^B2c Surveillance should include assessment of fatigue, functioning, mental health, treatment burden, and persistent post-infectious symptoms, with referral for supportive care when indicated. ^[100]^B2b^[202]^B2c

Surveillance priorities in CVID

Domain	Prevention or surveillance focus	Evidence
Infection prevention	Review breakthrough infections, adherence, tolerability, and IgRT route; consider IVIg or SCIg according to patient factors.	^[254]
COVID-19	Continue primary and booster vaccination; interpret humoral and cellular responses together.	^[65]^B2b^[173]^C4^[193]^B2b^[241]^C^[267]^C^[268]^[271]
Autoimmune cytopenia	Monitor platelet counts and bleeding symptoms, particularly in patients with prior autoimmune thrombocytopenia.	^[234]^B2b
Gastric cancer	Maintain specialist-directed upper gastrointestinal endoscopic surveillance and follow-up of precancerous lesions.	^[290]^C
Other malignancy	Continue age-appropriate screening and investigate lymphadenopathy, splenomegaly, weight loss, abnormal blood counts, or focal symptoms.	^[97]^C4^[108]^B3b^[291]
Tuberculosis	Review exposure and symptoms; use TST with repeat testing when initially 0–4 mm and obtain chest imaging when indicated.	^[248]^C
Long COVID and quality of life	Ask about persistent fatigue, respiratory, neurologic, and functional symptoms and assess psychosocial burden.	^[100]^B2b^[202]^B2c
Genetic risk	Consider targeted NGS when early onset, autoimmunity, low memory B cells, family history, or lymphoproliferation is present.	^[232]^C4

References

[1]
Unger S, Seidl M, van Schouwenburg P et al.. “The TH1 phenotype of follicular helper T cells indicates an IFN-γ-associated immune dysregulation in patients with CD21low common variable immunodeficiency.” The Journal of allergy and clinical immunology (2017). PMID: 28554560 ↗
L4TRIAL_NONRANDOMCited in: Definition, Classification & Hypersensitivity Mechanism Type
[2]
Jamee M, Zaki-Dizaji M, Lo B et al.. “Clinical, Immunological, and Genetic Features in Patients with Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) and IPEX-like Syndrome.” The journal of allergy and clinical immunology. In practice (2020). PMID: 32428713 ↗
L2SR_OBSCited in: Definition, Classification & Hypersensitivity Mechanism Type, Pathophysiology & Immune Mechanism, Clinical Presentation, Prognosis & Natural History
[3]
DiGiacomo DV, Roelstraete B, Lebwohl B et al.. “Predominantly antibody deficiency and the association with celiac disease in Sweden: A nationwide case-control study.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2024). PMID: 38331244 ↗
L3CASE_CONTROLCited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors
[4]
Kaplan B, Kopyltsova Y, Khokhar A et al.. “Rituximab and immune deficiency: case series and review of the literature.” The journal of allergy and clinical immunology. In practice (2014). PMID: 25213054 ↗
L4CASE_REPORTCited in: Definition, Classification & Hypersensitivity Mechanism Type, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[5]
Fedor ME, Rubinstein A. “Effects of long-term low-dose corticosteroid therapy on humoral immunity.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2006). PMID: 16892792 ↗
L4CASE_REPORTCited in: Definition, Classification & Hypersensitivity Mechanism Type, Acute Management & Anaphylaxis Pathway
[6]
Schwab C, Gabrysch A, Olbrich P et al.. “Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects.” The Journal of allergy and clinical immunology (2018). PMID: 29729943 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Complications, Comorbidities & Iatrogenic Risks
[7]
Magerus A, Rensing-Ehl A, Rao VK et al.. “Autoimmune lymphoproliferative immunodeficiencies (ALPIDs): A proposed approach to redefining ALPS and other lymphoproliferative immune disorders.” The Journal of allergy and clinical immunology (2023). PMID: 37977527 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[8]
Lorenzini T, Fliegauf M, Klammer N et al.. “Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations.” The Journal of allergy and clinical immunology (2020). PMID: 32278790 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Severity, Grading & Risk Stratification, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[9]
Jørgensen SF, Braadland PR, Ueland T et al.. “Tryptophan-kynurenine metabolites associate with inflammation and immunologic phenotypes in common variable immunodeficiency.” The Journal of allergy and clinical immunology (2025). PMID: 40378971 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Pathophysiology & Immune Mechanism, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Complications, Comorbidities & Iatrogenic Risks
[10]
Chinen J, Notarangelo LD, Shearer WT. “Advances in basic and clinical immunology in 2014.” The Journal of allergy and clinical immunology (2015). PMID: 25956014 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Hypersensitivity Mechanism Type, Pathophysiology & Immune Mechanism, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Prognosis & Natural History, Prevention, Screening & Surveillance
[11]
Tuijnenburg P, Lango Allen H, Burns SO et al.. “Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans.” The Journal of allergy and clinical immunology (2018). PMID: 29477724 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Complications, Comorbidities & Iatrogenic Risks, Prognosis & Natural History
[12]
Friedmann D, Payne KJ, Cousin V et al.. “Expansion of a distinct cytotoxic CD4 TFH-cell cluster in lymph nodes of patients with complicated common variable immunodeficiency.” The Journal of allergy and clinical immunology (2025). PMID: 41314478 ↗
L3OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type
[13]
Agondi RC, Barros MT, Rizzo LV et al.. “Allergic asthma in patients with common variable immunodeficiency.” Allergy (2009). PMID: 19839975 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[14]
DiGiacomo DV, Roelstraete B, Hammarström L et al.. “Predominant Antibody Deficiency and Risk of Microscopic Colitis: a Nationwide Case-Control Study in Sweden.” Journal of clinical immunology (2023). PMID: 37162615 ↗
L3CASE_CONTROLCited in: Definition, Classification & Hypersensitivity Mechanism Type
[15]
Seidel MG, Kindle G, Gathmann B et al.. “The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity.” The journal of allergy and clinical immunology. In practice (2019). PMID: 30776527 ↗
L5OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[16]
Bez P, Smits B, Geier C et al.. “Uncovering Risk Factors of Premature Mortality in Common Variable Immunodeficiency.” The journal of allergy and clinical immunology. In practice (2025). PMID: 40090481 ↗
L3OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Complications, Comorbidities & Iatrogenic Risks, Prognosis & Natural History
[17]
Ameratunga R, Edwards ESJ, Lehnert K et al.. “The Rapidly Expanding Genetic Spectrum of Common Variable Immunodeficiency-Like Disorders.” The journal of allergy and clinical immunology. In practice (2023). PMID: 36796510 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Severity, Grading & Risk Stratification, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[18]
Filion CA, Taylor-Black S, Maglione PJ et al.. “Differentiation of Common Variable Immunodeficiency From IgG Deficiency.” The journal of allergy and clinical immunology. In practice (2018). PMID: 30557717 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Pathophysiology & Immune Mechanism, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Complications, Comorbidities & Iatrogenic Risks
[19]
Elmoursi A, DiGiacomo DV, Farmer JR et al.. “Hepatic Manifestations in Common Variable Immunodeficiency Associated With Mortality and Worse Hospital Outcomes in Nationwide Analysis Using National Readmission Database.” The journal of allergy and clinical immunology. In practice (2025). PMID: 40998257 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors, Acute Management & Anaphylaxis Pathway, Complications, Comorbidities & Iatrogenic Risks
[20]
Agress A, Oprea Y, Roy S et al.. “The Association Between Malignancy, Immunodeficiency, and Atopy in IgE-Deficient Patients.” The journal of allergy and clinical immunology. In practice (2023). PMID: 37863316 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors
[21]
Ogershok PR, Hogan MB, Welch JE et al.. “Spectrum of illness in pediatric common variable immunodeficiency.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2006). PMID: 17165275 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Special Populations & Pregnancy
[22]
Ariue B, Patel NC, Bellanti JA. “Lessons from the American College of Allergy, Asthma and Immunology inborn errors of immunity survey: Advancing diagnostic and therapeutic strategies for the practicing allergist-immunologist.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2025). PMID: 41057108 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[23]
Lee WI, Huang JL, Kuo ML et al.. “Analysis of genetic defects in patients with the common variable immunodeficiency phenotype in a single Taiwanese tertiary care hospital.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2007). PMID: 18051214 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type
[24]
Ombrello MJ, Remmers EF, Sun G et al.. “Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions.” The New England journal of medicine (2012). PMID: 22236196 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Prognosis & Natural History
[25]
Park MA, Li JT, Hagan JB et al.. “Common variable immunodeficiency: a new look at an old disease.” Lancet (London, England) (2008). PMID: 18692715 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[26]
Urban B, Batlle-Masó L, Perurena-Prieto J et al.. “Heterozygous Predicted Loss-of-function Variants of TRAF3 in Patients with Common Variable Immunodeficiency.” Journal of clinical immunology (2024). PMID: 39579173 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[27]
Drabe CH, Laustsen MM, Marquart HV et al.. “Genetics in a Danish Common Variable Immunodeficiency Cohort.” Journal of clinical immunology (2025). PMID: 40455168 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[28]
Thoré P, Jaïs X, Savale L et al.. “Pulmonary Hypertension in Patients with Common Variable Immunodeficiency.” Journal of clinical immunology (2021). PMID: 34110542 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Prognosis & Natural History
[29]
Bargir UA, Setia P, Desai M et al.. “Common Variable Immunodeficiency Disorder: A Decade of Insights from a Cohort of 150 Patients in India and the Use of Machine Learning Algorithms to Predict Severity.” Journal of clinical immunology (2025). PMID: 40856873 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Severity, Grading & Risk Stratification, Complications, Comorbidities & Iatrogenic Risks, Special Populations & Pregnancy
[30]
Thouvenel CD, Tipton CM, Yamazaki Y et al.. “Hypomorphic RAG2 Deficiency Promotes Selection of Self-Reactive B Cells.” Journal of clinical immunology (2025). PMID: 39812873 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Pathophysiology & Immune Mechanism, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[31]
van Stigt AC, von der Thüsen JH, Mustafa DAM et al.. “Granulomas in Common Variable Immunodeficiency Display Different Histopathological Features Compared to Other Granulomatous Diseases.” Journal of clinical immunology (2024). PMID: 39373788 ↗
L3OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Prognosis & Natural History
[32]
Fortier JC, Haltigan E, Cavero-Chavez V et al.. “Clinical and Phenotypic Characterization of Common Variable Immunodeficiency Diagnosed in Younger and Older Adults.” Journal of clinical immunology (2022). PMID: 35588029 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Clinical Presentation, Complications, Comorbidities & Iatrogenic Risks, Prevention, Screening & Surveillance
[33]
Hägele P, Staus P, Scheible R et al.. “Diagnostic evaluation of paediatric autoimmune lymphoproliferative immunodeficiencies (ALPID): a prospective cohort study.” The Lancet. Haematology (2024). PMID: 38302222 ↗
L2COHORTCited in: Definition, Classification & Hypersensitivity Mechanism Type, Severity, Grading & Risk Stratification
[34]
Llobet MP, Soler-Palacin P, Detkova D et al.. “Common variable immunodeficiency: 20-yr experience at a single centre.” Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology (2008). PMID: 18798799 ↗
L4OTHERCited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Complications, Comorbidities & Iatrogenic Risks, Prognosis & Natural History, Prevention, Screening & Surveillance
[35]
Perez-Perez D, Santos-Argumedo L, Rodriguez-Alba JC et al.. “Analysis of LRBA pathogenic variants and the association with functional protein domains and clinical presentation.” Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology (2024). PMID: 38923448 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Hypersensitivity Mechanism Type, Pathophysiology & Immune Mechanism, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Severity, Grading & Risk Stratification
[36]
Costagliola G, De Marco E, Amato L et al.. “Sponge-like sonographic pattern of the spleen in immune dysregulation disorders.” Frontiers in immunology (2026). PMID: 42375368 ↗
L3CASE_REPORTCited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[37]
Endo Y, Koga T, Kurushima S et al.. “Case Report: Novel IRF2BP2 variant in a Japanese patient with impaired B-cell differentiation, Th1 polarization, and systemic immune dysregulation.” Frontiers in immunology (2025). PMID: 41246352 ↗
L4CASE_REPORTCited in: Definition, Classification & Hypersensitivity Mechanism Type, Clinical Presentation
[38]
Sormani J, Belot A, Nove-Josserand R et al.. “A New Variant in CTLA4 Highlights the Heterogeneous Phenotype of CTLA4 Haploinsufficiency.” Journal of clinical immunology (2025). PMID: 41219619 ↗
L4CASE_REPORTCited in: Definition, Classification & Hypersensitivity Mechanism Type, Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[39]
Nishikawa T, Tomomasa D, Hijikata A et al.. “Case Report: CD40LG Arg203Ile variant underlies atypical phenotype of X-linked hyper IgM syndrome.” Frontiers in immunology (2025). PMID: 40391217 ↗
L4CASE_REPORTCited in: Definition, Classification & Hypersensitivity Mechanism Type, Severity, Grading & Risk Stratification, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[40]
González-Torbay A, Reche-Yebra K, Clemente-Bernal Á et al.. “Functional insights of an uncommon hypomorphic variant in IL2RG as a monogenic cause of CVID-like disease with antibody deficiency and T CD4 lymphopenia.” Frontiers in immunology (2025). PMID: 40170851 ↗
L4CASE_REPORTCited in: Definition, Classification & Hypersensitivity Mechanism Type, Pathophysiology & Immune Mechanism
[41]
Ak B, Parıltay E, Gümüşburun R et al.. “Uniparental Disomy of Chromosome 4: A Case of Whole Chromosome UPD Presenting with LRBA Deficiency.” Journal of clinical immunology (2024). PMID: 39289195 ↗
L4CASE_REPORTCited in: Definition, Classification & Hypersensitivity Mechanism Type, Pathophysiology & Immune Mechanism
[42]
Le Coz C, Bengsch B, Khanna C et al.. “Common variable immunodeficiency-associated endotoxemia promotes early commitment to the T follicular lineage.” The Journal of allergy and clinical immunology (2019). PMID: 31445098 ↗
L4TRIAL_NONRANDOMCited in: Pathophysiology & Immune Mechanism, Epidemiology, Etiology & Risk Factors, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[43]
von Spee-Mayer C, Echternach C, Agarwal P et al.. “Abatacept Use Is Associated with Steroid Dose Reduction and Improvement in Fatigue and CD4-Dysregulation in CVID Patients with Interstitial Lung Disease.” The journal of allergy and clinical immunology. In practice (2020). PMID: 33223097 ↗
L2TRIAL_NONRANDOMCited in: Pathophysiology & Immune Mechanism, Acute Management & Anaphylaxis Pathway
[44]
Lang A, Agharahimi A, Vogel TP et al.. “From CVID to PIRD: Genetic Testing Leading to Signal Transducer and Activator of Transcription 3 Gain-of-Function Diagnosis and Directed Therapy.” The journal of allergy and clinical immunology. In practice (2026). PMID: 41999916 ↗
L4CASE_REPORTCited in: Pathophysiology & Immune Mechanism, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[45]
Agarwal S, Cunningham-Rundles C. “Thymoma and immunodeficiency (Good syndrome): a report of 2 unusual cases and review of the literature.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2007). PMID: 17304889 ↗
L4CASE_REPORTCited in: Pathophysiology & Immune Mechanism, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Prognosis & Natural History
[46]
Narula S, LaRosa DF, Kamoun M et al.. “Progressive multifocal leukoencephalopathy in a patient with common variable immunodeficiency and abnormal CD8+ T-cell subset distribution.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2007). PMID: 17521034 ↗
L4CASE_REPORTCited in: Pathophysiology & Immune Mechanism, Clinical Presentation
[47]
Udemgba C, Pillay B, Shafer S et al.. “IRF2BP2 deficiency: An important form of common variable immunodeficiency with inflammation.” The Journal of allergy and clinical immunology (2025). PMID: 40090425 ↗
L4OTHERCited in: Pathophysiology & Immune Mechanism, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[48]
Chinen J, Cowan MJ. “Advances and highlights in primary immunodeficiencies in 2017.” The Journal of allergy and clinical immunology (2018). PMID: 30170128 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Immune Mechanism, Epidemiology, Etiology & Risk Factors, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Acute Management & Anaphylaxis Pathway, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[49]
Abyazi ML, Bell KA, Gyimesi G et al.. “Convergence of cytokine dysregulation and antibody deficiency in common variable immunodeficiency with inflammatory complications.” The Journal of allergy and clinical immunology (2021). PMID: 34146579 ↗
L3OTHERCited in: Pathophysiology & Immune Mechanism, Epidemiology, Etiology & Risk Factors, Complications, Comorbidities & Iatrogenic Risks
[50]
Kaarbø M, Yang M, Hov JR et al.. “Duodenal inflammation in common variable immunodeficiency has altered transcriptional response to viruses.” The Journal of allergy and clinical immunology (2022). PMID: 36220400 ↗
L3OTHERCited in: Pathophysiology & Immune Mechanism
[51]
Le Coz C, Trofa M, Butler DL et al.. “The common variable immunodeficiency IgM repertoire narrowly recognizes erythrocyte and platelet glycans.” The Journal of allergy and clinical immunology (2024). PMID: 38692308 ↗
L4OTHERCited in: Pathophysiology & Immune Mechanism
[52]
Ho HE, Radigan L, Qi J et al.. “Bruton tyrosine kinase modulates systemic immune activation to bacterial translocation in primary antibody deficiencies.” The Journal of allergy and clinical immunology (2025). PMID: 41033468 ↗
L2OTHERCited in: Pathophysiology & Immune Mechanism
[53]
Boast B, Goel S, González-Granado LI et al.. “TCF3 haploinsufficiency defined by immune, clinical, gene-dosage, and murine studies.” The Journal of allergy and clinical immunology (2023). PMID: 37277074 ↗
L4OTHERCited in: Pathophysiology & Immune Mechanism, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[54]
Urdea D, Mereuta DV, Iorga RE et al.. “Concurrent hereditary angioedema type I and common variable immunodeficiency presenting as suspected antibiotic hypersensitivity: Case report and literature discussion.” The World Allergy Organization journal (2026). PMID: 42221876 ↗
L4CASE_REPORTCited in: Pathophysiology & Immune Mechanism, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Severity, Grading & Risk Stratification, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[55]
Friedmann D, Goldacker S, Peter HH et al.. “Preserved Cellular Immunity Upon Influenza Vaccination in Most Patients with Common Variable Immunodeficiency.” The journal of allergy and clinical immunology. In practice (2020). PMID: 32330665 ↗
L2OTHERCited in: Pathophysiology & Immune Mechanism, Acute Management & Anaphylaxis Pathway, Prevention, Screening & Surveillance
[56]
Schussler E, Beasley MB, Maglione PJ. “Lung Disease in Primary Antibody Deficiencies.” The journal of allergy and clinical immunology. In practice (2016). PMID: 27836055 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Immune Mechanism, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Complications, Comorbidities & Iatrogenic Risks, Prevention, Screening & Surveillance
[57]
Yin J, Hayes KM, Ong MS et al.. “Common Variable Immunodeficiency Clinical Manifestations Are Shaped by Presence and Type of Heterozygous NFKB1 Variants.” The journal of allergy and clinical immunology. In practice (2024). PMID: 39672378 ↗
L2OTHERCited in: Pathophysiology & Immune Mechanism, Epidemiology, Etiology & Risk Factors, Complications, Comorbidities & Iatrogenic Risks
[58]
Ameratunga R, Longhurst H, Steele R et al.. “Common Variable Immunodeficiency Disorders, T-Cell Responses to SARS-CoV-2 Vaccines, and the Risk of Chronic COVID-19.” The journal of allergy and clinical immunology. In practice (2021). PMID: 34182162 ↗
L5OTHERCited in: Pathophysiology & Immune Mechanism, Severity, Grading & Risk Stratification, Acute Management & Anaphylaxis Pathway, Prevention, Screening & Surveillance
[59]
Milota T, Smetanova J, Skotnicova A et al.. “Clinical Outcomes, Immunogenicity, and Safety of BNT162b2 Vaccine in Primary Antibody Deficiency.” The journal of allergy and clinical immunology. In practice (2022). PMID: 36379409 ↗
L2OTHERCited in: Pathophysiology & Immune Mechanism, Epidemiology, Etiology & Risk Factors, Severity, Grading & Risk Stratification, Complications, Comorbidities & Iatrogenic Risks, Prevention, Screening & Surveillance
[60]
van de Ven A, Mader I, Wolff D et al.. “Structural Noninfectious Manifestations of the Central Nervous System in Common Variable Immunodeficiency Disorders.” The journal of allergy and clinical immunology. In practice (2019). PMID: 31857261 ↗
L4OTHERCited in: Pathophysiology & Immune Mechanism
[61]
Agarwal S, Cunningham-Rundles C. “Autoimmunity in common variable immunodeficiency.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2019). PMID: 31349011 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Immune Mechanism, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Complications, Comorbidities & Iatrogenic Risks, Prognosis & Natural History
[62]
Durkee-Shock JR, Keller MD. “Immunizing the imperfect immune system: Coronavirus disease 2019 vaccination in patients with inborn errors of immunity.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2022). PMID: 35718282 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Immune Mechanism, Epidemiology, Etiology & Risk Factors, Acute Management & Anaphylaxis Pathway, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Prevention, Screening & Surveillance
[63]
Ballow M. “Managing comorbid complications in patients with common variable immunodeficiency.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2013). PMID: 24267402 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Immune Mechanism, Complications, Comorbidities & Iatrogenic Risks
[64]
Maglione PJ, Overbey JR, Radigan L et al.. “Pulmonary radiologic findings in common variable immunodeficiency: clinical and immunological correlations.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2014). PMID: 24880814 ↗
L4OTHERCited in: Pathophysiology & Immune Mechanism, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[65]
Rosenthal JA, Papa MP, Sanz M et al.. “Antibody and T-cell responses to coronavirus disease 2019 vaccination in common variable immunodeficiency and specific antibody deficiency.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2023). PMID: 36736722 ↗
L2OTHERCited in: Pathophysiology & Immune Mechanism, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Acute Management & Anaphylaxis Pathway, Prevention, Screening & Surveillance
[66]
Hashiguchi S, Tomomasa D, Nishikawa T et al.. “18q Deletion Syndrome Presenting with Late-Onset Combined Immunodeficiency.” Journal of clinical immunology (2024). PMID: 38896123 ↗
L4CASE_REPORTCited in: Pathophysiology & Immune Mechanism
[67]
Vossen MG, Kartnig F, Mrak D et al.. “Humoral and cellular response to the third COVID-19 vaccination in patients with inborn errors of immunity or mannose-binding lectin deficiency : A prospective controlled open-label trial.” Wiener klinische Wochenschrift (2024). PMID: 39446203 ↗
L2RCTCited in: Pathophysiology & Immune Mechanism, Acute Management & Anaphylaxis Pathway
[68]
Yel L. “Selective IgA deficiency.” Journal of clinical immunology (2010). PMID: 20101521 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Immune Mechanism, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Acute Management & Anaphylaxis Pathway
[69]
Cunningham-Rundles C. “Autoimmune manifestations in common variable immunodeficiency.” Journal of clinical immunology (2008). PMID: 18322785 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Immune Mechanism
[70]
Strohmeier V, Andrieux G, Unger S et al.. “Interferon-Driven Immune Dysregulation in Common Variable Immunodeficiency-Associated Villous Atrophy and Norovirus Infection.” Journal of clinical immunology (2022). PMID: 36282455 ↗
L2OTHERCited in: Pathophysiology & Immune Mechanism, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Severity, Grading & Risk Stratification
[71]
Sekinaka Y, Mitsuiki N, Imai K et al.. “Common Variable Immunodeficiency Caused by FANC Mutations.” Journal of clinical immunology (2017). PMID: 28493158 ↗
L4OTHERCited in: Pathophysiology & Immune Mechanism, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[72]
Arroyo-Sánchez D, Cabrera-Marante O, Laguna-Goya R et al.. “Immunogenicity of Anti-SARS-CoV-2 Vaccines in Common Variable Immunodeficiency.” Journal of clinical immunology (2021). PMID: 34787773 ↗
L4OTHERCited in: Pathophysiology & Immune Mechanism, Acute Management & Anaphylaxis Pathway, Prevention, Screening & Surveillance
[73]
Rodríguez-Cortez VC, Del Pino-Molina L, Rodríguez-Ubreva J et al.. “Dissecting Epigenetic Dysregulation of Primary Antibody Deficiencies.” Journal of clinical immunology (2016). PMID: 26984849 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Immune Mechanism
[74]
Hel Z, Huijbregts RP, Xu J et al.. “Altered serum cytokine signature in common variable immunodeficiency.” Journal of clinical immunology (2014). PMID: 25246148 ↗
L3OTHERCited in: Pathophysiology & Immune Mechanism
[75]
Yang M, Kaarbø M, Myhre V et al.. “Altered Genome-Wide DNA Methylation in the Duodenum of Common Variable Immunodeficiency Patients.” Journal of clinical immunology (2024). PMID: 38780872 ↗
L4OTHERCited in: Pathophysiology & Immune Mechanism
[76]
Soltani M, Rezaei M, Fekrvand S et al.. “Role of rare immune cells in common variable immunodeficiency.” Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology (2022). PMID: 34937129 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Immune Mechanism, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[77]
Yong PL, Orange JS, Sullivan KE. “Pediatric common variable immunodeficiency: immunologic and phenotypic associations with switched memory B cells.” Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology (2010). PMID: 20337966 ↗
L2OTHERCited in: Pathophysiology & Immune Mechanism, Special Populations & Pregnancy, Prevention, Screening & Surveillance
[78]
Lenti MV, Savioli J, Achilli G et al.. “Autoimmune diseases associated with common variable immune deficiency.” Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology (2020). PMID: 33236426 ↗
L5OTHERCited in: Pathophysiology & Immune Mechanism, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Acute Management & Anaphylaxis Pathway, Complications, Comorbidities & Iatrogenic Risks
[79]
Kutukculer N, Gulez N. “The outcome of patients with unclassified hypogammaglobulinemia in early childhood.” Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology (2009). PMID: 19196447 ↗
L4OTHERCited in: Pathophysiology & Immune Mechanism, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Prognosis & Natural History
[80]
Tegtmeyer D, Seidl M, Gerner P et al.. “Inflammatory bowel disease caused by primary immunodeficiencies-Clinical presentations, review of literature, and proposal of a rational diagnostic algorithm.” Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology (2017). PMID: 28513998 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Immune Mechanism, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[81]
Zeng W, Feng X, Liang B et al.. “Good syndrome presenting with multiple pulmonary infections: a case report involving metagenomic sequencing diagnosis.” Frontiers in medicine (2025). PMID: 40904363 ↗
L4CASE_REPORTCited in: Pathophysiology & Immune Mechanism, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Prognosis & Natural History
[82]
Consolini R, Maestrini G, Abu-Rumeileh S et al.. “The Intertwining Between Arthritis and Inborn Errors of Immunity.” Journal of clinical medicine (2026). PMID: 42123030 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Immune Mechanism
[83]
Yang M, Kaarbø M, Myhre V et al.. “Distinct Proteomic and Transcriptomic Profiles in T-cells and Monocytes in Patients with Common Variable Immunodeficiency: an Exploratory Study.” Journal of clinical immunology (2026). PMID: 41991796 ↗
L3OTHERCited in: Pathophysiology & Immune Mechanism, Epidemiology, Etiology & Risk Factors, Complications, Comorbidities & Iatrogenic Risks
[84]
Comans SET, Sprenkeler EGG, Koenen MH et al.. “Familial patterns of immune dysregulation in CVID: insights from B- and T-cell phenotyping and antibody profiling.” Frontiers in immunology (2026). PMID: 41909677 ↗
L4OTHERCited in: Pathophysiology & Immune Mechanism, Prevention, Screening & Surveillance
[85]
Briassouli E, Marinakis N, Spoulou V et al.. “IL2RG-related immunodeficiencies: from SCID to atypical presentations.” Frontiers in immunology (2026). PMID: 41909668 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Immune Mechanism, Prognosis & Natural History
[86]
Fekrvand S, Abolhassani H, Esfahani ZH et al.. “Cancer Trends in Inborn Errors of Immunity: A Systematic Review and Meta-Analysis.” Journal of clinical immunology (2024). PMID: 39466473 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Prognosis & Natural History
[87]
Egg D, Rump IC, Mitsuiki N et al.. “Therapeutic options for CTLA-4 insufficiency.” The Journal of allergy and clinical immunology (2021). PMID: 34111452 ↗
L4OTHERCited in: Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Severity, Grading & Risk Stratification, Acute Management & Anaphylaxis Pathway, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Complications, Comorbidities & Iatrogenic Risks, Prevention, Screening & Surveillance
[88]
Torres-Valle A, Neirinck J, Silva SL et al.. “Immunologic biomarkers of noninfectious complications and overall survival in common variable immunodeficiency.” The Journal of allergy and clinical immunology (2025). PMID: 41176068 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Severity, Grading & Risk Stratification, Complications, Comorbidities & Iatrogenic Risks, Prognosis & Natural History
[89]
Gray PE, David C. “Inborn Errors of Immunity and Autoimmune Disease.” The journal of allergy and clinical immunology. In practice (2023). PMID: 37119983 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Prognosis & Natural History
[90]
Jolles S. “The variable in common variable immunodeficiency: a disease of complex phenotypes.” The journal of allergy and clinical immunology. In practice (2013). PMID: 24565700 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Severity, Grading & Risk Stratification, Acute Management & Anaphylaxis Pathway, Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics, Complications, Comorbidities & Iatrogenic Risks
[91]
Cunningham-Rundles C. “Current concepts: Common variable immunodeficiency.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2025). PMID: 41274495 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors, Complications, Comorbidities & Iatrogenic Risks
[92]
Moazzami B, Mohayeji Nasrabadi MA, Abolhassani H et al.. “Comprehensive assessment of respiratory complications in patients with common variable immunodeficiency.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2020). PMID: 32007567 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Complications, Comorbidities & Iatrogenic Risks, Prognosis & Natural History
[93]
Ferastraoaru D, Gross R, Rosenstreich D. “Increased malignancy incidence in IgE deficient patients not due to concomitant Common Variable Immunodeficiency.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2017). PMID: 28778662 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[94]
De Renzis C, Gambier RF, Gigante A et al.. “Chronic Kidney Disease in Common Variable Immunodeficiency: a Multicenter Study.” Journal of clinical immunology (2025). PMID: 40407942 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[95]
van der Poorten DK, McLeod D, Ahlenstiel G et al.. “Gastric Cancer Screening in Common Variable Immunodeficiency.” Journal of clinical immunology (2018). PMID: 30219982 ↗
L3OTHERCited in: Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Prevention, Screening & Surveillance
[96]
Garcia-Prat M, Batlle-Masó L, Parra-Martínez A et al.. “Role of Skewed X-Chromosome Inactivation in Common Variable Immunodeficiency.” Journal of clinical immunology (2024). PMID: 38265673 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors
[97]
Gumusburun R, Yıldırım O, Karakoc M et al.. “Malignancy in Adults with Inborn Errors of Immunity: A Retrospective Single-Center Study.” Journal of clinical immunology (2025). PMID: 40993321 ↗
L4OTHERCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Complications, Comorbidities & Iatrogenic Risks, Prevention, Screening & Surveillance
[98]
Punj M, Neshat SS, Mateus AYL et al.. “Assessment of Sleep Disorders in Patients with CVID.” Journal of clinical immunology (2024). PMID: 38676767 ↗
L4OTHERCited in: Epidemiology, Etiology & Risk Factors, Severity, Grading & Risk Stratification, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Complications, Comorbidities & Iatrogenic Risks
[99]
Sperlich JM, Grimbacher B, Soetedjo V et al.. “Predictive Factors for and Complications of Bronchiectasis in Common Variable Immunodeficiency Disorders.” Journal of clinical immunology (2022). PMID: 35015197 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Complications, Comorbidities & Iatrogenic Risks
[100]
Villa A, Milito C, Deiana CM et al.. “High Prevalence of Long COVID in Common Variable Immunodeficiency: An Italian Multicentric Study.” Journal of clinical immunology (2024). PMID: 38319477 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Prevention, Screening & Surveillance
[101]
Puzenat DT, Cheminant M, Dannaoui E et al.. “Cryptosporidiosis in Ptients with Inborn Errors of Immunity: Retrospective cohort study of the French National Reference Center (CEREDIH).” The Journal of infectious diseases (2026). PMID: 42378670 ↗
L3COHORTCited in: Epidemiology, Etiology & Risk Factors, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Complications, Comorbidities & Iatrogenic Risks
[102]
Miranda-Bautista J, Martínez-Lozano H, Di Natale M et al.. “The Prognostic Impact of Enteropathy and Liver Disease in Common Variable Immunodeficiency: A Retrospective Cohort Study.” Clinical and translational gastroenterology (2026). PMID: 41324469 ↗
L3COHORTCited in: Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[103]
Dogru D, Dogru Y, Atschekzei F et al.. “Reappraisal of IgG subclass deficiencies: a retrospective comparative cohort study.” Frontiers in immunology (2025). PMID: 40313941 ↗
L3COHORTCited in: Epidemiology, Etiology & Risk Factors
[104]
Cekic S, Metin A, Aytekin C et al.. “The evaluation of malignancies in Turkish primary immunodeficiency patients; a multicenter study.” Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology (2020). PMID: 32060950 ↗
L4OTHERCited in: Epidemiology, Etiology & Risk Factors, Prognosis & Natural History
[105]
Baris S, Ozen A, Ercan H et al.. “Osteoporosis: an ignored complication of CVID.” Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology (2011). PMID: 21645119 ↗
L4OTHERCited in: Epidemiology, Etiology & Risk Factors, Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Severity, Grading & Risk Stratification
[106]
Azizi G, Tavakol M, Yazdani R et al.. “Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity.” Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology (2021). PMID: 33774840 ↗
L3OTHERCited in: Epidemiology, Etiology & Risk Factors, Clinical Presentation, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Complications, Comorbidities & Iatrogenic Risks
[107]
Zhang J, Cai H, Zhu T et al.. “Clinical, genetic, and functional characterization of novel NFKB1 variants in Chinese patients with primary immunodeficiency.” Clinical and experimental immunology (2026). PMID: 42252100 ↗
L4OTHERCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Complications, Comorbidities & Iatrogenic Risks
[108]
Wenger TA, Collet C, West J et al.. “Rates and Outcomes of Head and Neck Cancer Among Patients With Primary Immunodeficiency Disorders.” Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery (2026). PMID: 42171009 ↗
L3OTHERCited in: Epidemiology, Etiology & Risk Factors, Complications, Comorbidities & Iatrogenic Risks, Prevention, Screening & Surveillance
[109]
Martinez T, Grand Z, Garcia S et al.. “A global perspective on autoimmunity and immunodeficiency: exploring geoepidemiology trends.” Current opinion in immunology (2026). PMID: 41980333 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors
[110]
Romberg N, Le Coz C, Glauzy S et al.. “Patients with common variable immunodeficiency with autoimmune cytopenias exhibit hyperplastic yet inefficient germinal center responses.” The Journal of allergy and clinical immunology (2018). PMID: 29935219 ↗
L3TRIAL_NONRANDOMCited in: Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Prognosis & Natural History
[111]
Bonilla FA, Barlan I, Chapel H et al.. “International Consensus Document (ICON): Common Variable Immunodeficiency Disorders.” The journal of allergy and clinical immunology. In practice (2015). PMID: 26563668 ↗
L1OTHERCited in: Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[112]
Mayampurath A, Ajith A, Anderson-Smits C et al.. “Early Diagnosis of Primary Immunodeficiency Disease Using Clinical Data and Machine Learning.” The journal of allergy and clinical immunology. In practice (2022). PMID: 36108921 ↗
L3OTHERCited in: Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Prognosis & Natural History
[113]
DeVries AS, Harper J, Murray A et al.. “Vaccine-derived poliomyelitis 12 years after infection in Minnesota.” The New England journal of medicine (2011). PMID: 21675890 ↗
L4CASE_REPORTCited in: Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[114]
Lee TK, Gereige JD, Maglione PJ. “State-of-the-art diagnostic evaluation of common variable immunodeficiency.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2021). PMID: 33716149 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Complications, Comorbidities & Iatrogenic Risks, Prognosis & Natural History
[115]
Izadi N, Knight V, Strand M et al.. “An enzyme-linked immunospot assay to evaluate Pneumovax response when on intravenous immunoglobulin.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2021). PMID: 34391898 ↗
L4OTHERCited in: Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[116]
Hartono S, Motosue MS, Khan S et al.. “Predictors of granulomatous lymphocytic interstitial lung disease in common variable immunodeficiency.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2017). PMID: 28254202 ↗
L3OTHERCited in: Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[117]
Kuehn HS, Boisson B, Cunningham-Rundles C et al.. “Loss of B Cells in Patients with Heterozygous Mutations in IKAROS.” The New England journal of medicine (2016). PMID: 26981933 ↗
L4OTHERCited in: Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Prevention, Screening & Surveillance
[118]
Touw CM, van de Ven AA, de Jong PA et al.. “Detection of pulmonary complications in common variable immunodeficiency.” Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology (2009). PMID: 19912551 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Complications, Comorbidities & Iatrogenic Risks, Prognosis & Natural History
[119]
Reznik EV, Iarovoi MD, Romanova TS et al.. “Prolonged Infections and Inflammatory Diseases in Common Variable Immune Deficiency as a Cause of AA Amyloidosis.” Journal of clinical medicine (2026). PMID: 42278892 ↗
L4CASE_REPORTCited in: Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[120]
Hbibi M, Elamine A, Benhsaien I et al.. “Case Report: Different faces of LRBA deficiency in five Moroccan families.” Frontiers in immunology (2026). PMID: 42148132 ↗
L4CASE_REPORTCited in: Clinical Presentation, Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[121]
Varenne F, Siegfried-Vergnon A, Lhomme S et al.. “JC Virus-Related Retinopathy.” JAMA ophthalmology (2025). PMID: 40674067 ↗
L4CASE_REPORTCited in: Clinical Presentation, Acute Management & Anaphylaxis Pathway, Prognosis & Natural History
[122]
Schwitzguébel AJ, Jandus P, Lacroix JS et al.. “Immunoglobulin deficiency in patients with chronic rhinosinusitis: Systematic review of the literature and meta-analysis.” The Journal of allergy and clinical immunology (2015). PMID: 26329513 ↗
L1SR_OBSCited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[123]
Jerschow E, De Vos GS, Hudes G et al.. “A case of common variable immunodeficiency syndrome associated with Takayasu arteritis.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2007). PMID: 17304891 ↗
L4CASE_REPORTCited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[124]
Renz H. “Advances in in vitro diagnostics in allergy, asthma, and immunology in 2012.” The Journal of allergy and clinical immunology (2013). PMID: 24139605 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Acute Management & Anaphylaxis Pathway, Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics, Prevention, Screening & Surveillance
[125]
Sperlich JM, Grimbacher B, Workman S et al.. “Respiratory Infections and Antibiotic Usage in Common Variable Immunodeficiency.” The journal of allergy and clinical immunology. In practice (2017). PMID: 28734862 ↗
L4OTHERCited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[126]
Hurst JR, Verma N, Lowe D et al.. “British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders.” The journal of allergy and clinical immunology. In practice (2017). PMID: 28351785 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Severity, Grading & Risk Stratification, Complications, Comorbidities & Iatrogenic Risks
[127]
Maglione PJ, Ko HM, Tokuyama M et al.. “Serum B-Cell Maturation Antigen (BCMA) Levels Differentiate Primary Antibody Deficiencies.” The journal of allergy and clinical immunology. In practice (2019). PMID: 31430592 ↗
L4OTHERCited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Prognosis & Natural History
[128]
Maglione PJ, Overbey JR, Cunningham-Rundles C. “Progression of Common Variable Immunodeficiency Interstitial Lung Disease Accompanies Distinct Pulmonary and Laboratory Findings.” The journal of allergy and clinical immunology. In practice (2015). PMID: 26372540 ↗
L2OTHERCited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[129]
Roa-Bautista A, Brown LK, Tadros S et al.. “Clinical Features, Immunological Characteristics, and Treatment Outcomes of Campylobacter spp. Infections in Patients With Common Variable Immunodeficiency.” The journal of allergy and clinical immunology. In practice (2023). PMID: 37406804 ↗
L2OTHERCited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Prognosis & Natural History
[130]
Busse PJ, Farzan S, Cunningham-Rundles C. “Pulmonary complications of common variable immunodeficiency.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2007). PMID: 17225714 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Complications, Comorbidities & Iatrogenic Risks, Prognosis & Natural History
[131]
Deyà-Martínez A, Esteve-Solé A, Vélez-Tirado N et al.. “Sirolimus as an alternative treatment in patients with granulomatous-lymphocytic lung disease and humoral immunodeficiency with impaired regulatory T cells.” Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology (2018). PMID: 29532571 ↗
L4CASE_REPORTCited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Complications, Comorbidities & Iatrogenic Risks, Prognosis & Natural History
[132]
Lopes-da-Silva S, Rizzo LV. “Autoimmunity in common variable immunodeficiency.” Journal of clinical immunology (2008). PMID: 18443901 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Prognosis & Natural History, Prevention, Screening & Surveillance
[133]
Shapiro RS, Wasserman RL, Bonagura V et al.. “Emerging Paradigm of Primary Immunodeficiency Disease: Individualizing Immunoglobulin Dose and Delivery to Enhance Outcomes.” Journal of clinical immunology (2014). PMID: 24477950 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Acute Management & Anaphylaxis Pathway, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[134]
Hoernes M, Seger R, Reichenbach J. “Modern management of primary B-cell immunodeficiencies.” Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology (2011). PMID: 22122788 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Acute Management & Anaphylaxis Pathway, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Complications, Comorbidities & Iatrogenic Risks
[135]
Palmeira P, Costa-Carvalho BT, Arslanian C et al.. “Transfer of antibodies across the placenta and in breast milk from mothers on intravenous immunoglobulin.” Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology (2009). PMID: 19220771 ↗
L4OTHERCited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Special Populations & Pregnancy
[136]
Stojanovic M, Stojkovic-Lalosevic M, Stankovic S et al.. “Non-invasive assessment of hepatic involvement in common variable immunodeficiency and agammaglobulinemia using enhanced liver fibrosis score and shearwave elastography.” Frontiers in immunology (2026). PMID: 42421971 ↗
L4OTHERCited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[137]
Elmoursi A, Charlier C, Cunningham-Rundles C et al.. “Insights into Clinical Challenges and Management of Primary and Secondary Antibody Deficiency in Pregnancy.” The journal of allergy and clinical immunology. In practice (2026). PMID: 42250902 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Complications, Comorbidities & Iatrogenic Risks, Prognosis & Natural History, Special Populations & Pregnancy, Prevention, Screening & Surveillance
[138]
Matson EM, Ware MS, Feng F et al.. “Coexistent alterations of BAFF and B-cell phenotypes in complicated CVID course.” The Journal of allergy and clinical immunology (2026). PMID: 42219089 ↗
L4OTHERCited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup, Complications, Comorbidities & Iatrogenic Risks, Prognosis & Natural History
[139]
Smits B, Goldacker S, Seneviratne S et al.. “The efficacy and safety of systemic corticosteroids as first line treatment for granulomatous lymphocytic interstitial lung disease.” The Journal of allergy and clinical immunology (2022). PMID: 36587851 ↗
L4RCTCited in: Severity, Grading & Risk Stratification, Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics, Complications, Comorbidities & Iatrogenic Risks, Prognosis & Natural History
[140]
Gardulf A, Abolhassani H, Gustafson R et al.. “Predictive markers for humoral influenza vaccine response in patients with common variable immunodeficiency.” The Journal of allergy and clinical immunology (2018). PMID: 29678747 ↗
L4TRIAL_NONRANDOMCited in: Severity, Grading & Risk Stratification, Complications, Comorbidities & Iatrogenic Risks, Prognosis & Natural History
[141]
Chase NM, Verbsky JW, Hintermeyer MK et al.. “Use of combination chemotherapy for treatment of granulomatous and lymphocytic interstitial lung disease (GLILD) in patients with common variable immunodeficiency (CVID).” Journal of clinical immunology (2012). PMID: 22930256 ↗
L4RCTCited in: Severity, Grading & Risk Stratification, Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics
[142]
Bergman P, Wullimann D, Gao Y et al.. “Elevated CD21low B Cell Frequency Is a Marker of Poor Immunity to Pfizer-BioNTech BNT162b2 mRNA Vaccine Against SARS-CoV-2 in Patients with Common Variable Immunodeficiency.” Journal of clinical immunology (2022). PMID: 35290571 ↗
L2TRIAL_NONRANDOMCited in: Severity, Grading & Risk Stratification
[143]
Mandola AB, Sharfe N, Nagdi Z et al.. “Combined immunodeficiency caused by a novel homozygous NFKB1 mutation.” The Journal of allergy and clinical immunology (2020). PMID: 32980423 ↗
L4CASE_REPORTCited in: Severity, Grading & Risk Stratification
[144]
Abraham RS, Marshall JM, Kuehn HS et al.. “Severe SARS-CoV-2 disease in the context of a NF-κB2 loss-of-function pathogenic variant.” The Journal of allergy and clinical immunology (2020). PMID: 33007327 ↗
L4CASE_REPORTCited in: Severity, Grading & Risk Stratification, Acute Management & Anaphylaxis Pathway, Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics, Prognosis & Natural History
[145]
Materne E, Zhou B, DiGiacomo D et al.. “Renal complications in patients with predominantly antibody deficiency in the United States Immune Deficiency Network (USIDNET).” The Journal of allergy and clinical immunology (2024). PMID: 38555979 ↗
L2OTHERCited in: Severity, Grading & Risk Stratification
[146]
Hennig C, Ilginus C, Boztug K et al.. “High-content cytometry and transcriptomic biomarker profiling of human B-cell activation.” The Journal of allergy and clinical immunology (2013). PMID: 24012209 ↗
L5OTHERCited in: Severity, Grading & Risk Stratification
[147]
Bintalib HM, van de Ven AAJM, Rojas-Reyes MX et al.. “Clinical Practice Guideline for the diagnosis of Granulomatous-Lymphocytic Interstitial Lung Disease (GLILD) in patients with Common Variable Immunodeficiency Disorders (CVID) - an ERS Clinical Research Collaboration.” The European respiratory journal (2026). PMID: 42350065 ↗
L1GUIDELINECited in: Severity, Grading & Risk Stratification, Prognosis & Natural History
[148]
Smits BM, Boland SL, Hol ME et al.. “Pulmonary Computed Tomography Screening Frequency in Primary Antibody Deficiency.” The journal of allergy and clinical immunology. In practice (2024). PMID: 38182096 ↗
L2OTHERCited in: Severity, Grading & Risk Stratification
[149]
Yazdani R, Abolhassani H, Kiaee F et al.. “Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort.” The journal of allergy and clinical immunology. In practice (2018). PMID: 30240888 ↗
L2OTHERCited in: Severity, Grading & Risk Stratification, Prognosis & Natural History
[150]
D'Silva SJ, Patrie J, Noonan E et al.. “Undetectable IgE association with noninfectious complications of common variable immune deficiency.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2025). PMID: 41390140 ↗
L2OTHERCited in: Severity, Grading & Risk Stratification, Complications, Comorbidities & Iatrogenic Risks
[151]
Boztug H, Hirschmugl T, Holter W et al.. “NF-κB1 Haploinsufficiency Causing Immunodeficiency and EBV-Driven Lymphoproliferation.” Journal of clinical immunology (2016). PMID: 27338827 ↗
L4CASE_REPORTCited in: Severity, Grading & Risk Stratification
[152]
Slade CA, McLean C, Scerri T et al.. “Fatal Enteroviral Encephalitis in a Patient with Common Variable Immunodeficiency Harbouring a Novel Mutation in NFKB2.” Journal of clinical immunology (2019). PMID: 30927119 ↗
L4CASE_REPORTCited in: Severity, Grading & Risk Stratification
[153]
Karafotias I, Martini H, Lee CV et al.. “CXCL13 as a Biomarker of Complex Common Variable Immunodeficiency.” Journal of clinical immunology (2025). PMID: 41288852 ↗
L3OTHERCited in: Severity, Grading & Risk Stratification
[154]
Bergmans B, Fontane Pennock-Janssen L, van Puijenbroek E et al.. “Exploring the Pathogens in Primary Predominantly Antibody Deficiencies of Unknown Genetic Origin.” Journal of clinical immunology (2025). PMID: 41384995 ↗
L2OTHERCited in: Severity, Grading & Risk Stratification, Prognosis & Natural History
[155]
Katzenstein TL, Rasmussen LD, Drabe CH et al.. “Outcome of SARS-CoV-2 infection among patients with common variable immunodeficiency and a matched control group: A Danish nationwide cohort study.” Frontiers in immunology (2022). PMID: 36211430 ↗
L2COHORTCited in: Severity, Grading & Risk Stratification
[156]
Danieli MG, Verga JU, Mezzanotte C et al.. “Replacement and Immunomodulatory Activities of 20% Subcutaneous Immunoglobulin Treatment: A Single-Center Retrospective Study in Autoimmune Myositis and CVID Patients.” Frontiers in immunology (2022). PMID: 35111165 ↗
L4COHORTCited in: Severity, Grading & Risk Stratification, Acute Management & Anaphylaxis Pathway
[157]
Russo R, Andolfo I, Lasorsa VA et al.. “The TNFRSF13C H159Y Variant Is Associated with Severe COVID-19: A Retrospective Study of 500 Patients from Southern Italy.” Genes (2021). PMID: 34201032 ↗
L3COHORTCited in: Severity, Grading & Risk Stratification
[158]
van der Heijden J, Geissler J, van Mirre E et al.. “A novel splice variant of FcγRIIa: a risk factor for anaphylaxis in patients with hypogammaglobulinemia.” The Journal of allergy and clinical immunology (2013). PMID: 23545275 ↗
L4CASE_REPORTCited in: Acute Management & Anaphylaxis Pathway
[159]
Arora R, Newton TC, Nelson MR. “Subcutaneous immunoglobulin therapy in an 11-year-old patient with common variable immunodeficiency and von Willebrand disease.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2007). PMID: 17941286 ↗
L4CASE_REPORTCited in: Acute Management & Anaphylaxis Pathway, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Complications, Comorbidities & Iatrogenic Risks, Special Populations & Pregnancy
[160]
Chinen J, Notarangelo LD, Shearer WT. “Advances in clinical immunology in 2015.” The Journal of allergy and clinical immunology (2016). PMID: 27931534 ↗
L5REVIEW_NARRATIVECited in: Acute Management & Anaphylaxis Pathway, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[161]
Chinen J, Badran YR, Geha RS et al.. “Advances in basic and clinical immunology in 2016.” The Journal of allergy and clinical immunology (2017). PMID: 28826774 ↗
L5REVIEW_NARRATIVECited in: Acute Management & Anaphylaxis Pathway, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[162]
Bonilla FA, Geha RS. “2. Update on primary immunodeficiency diseases.” The Journal of allergy and clinical immunology (2006). PMID: 16455342 ↗
L5REVIEW_NARRATIVECited in: Acute Management & Anaphylaxis Pathway, Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[163]
Gathmann B, Mahlaoui N, Gérard L et al.. “Clinical picture and treatment of 2212 patients with common variable immunodeficiency.” The Journal of allergy and clinical immunology (2014). PMID: 24582312 ↗
L2OTHERCited in: Acute Management & Anaphylaxis Pathway
[164]
Wehr C, Gennery AR, Lindemans C et al.. “Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency.” The Journal of allergy and clinical immunology (2015). PMID: 25595268 ↗
L4OTHERCited in: Acute Management & Anaphylaxis Pathway
[165]
Pulvirenti F, Cinetto F, Milito C et al.. “Health-Related Quality of Life in Common Variable Immunodeficiency Italian Patients Switched to Remote Assistance During the COVID-19 Pandemic.” The journal of allergy and clinical immunology. In practice (2020). PMID: 32278865 ↗
L4OTHERCited in: Acute Management & Anaphylaxis Pathway
[166]
Zuzolo J, Zulfiqar MF, Spoelhof B et al.. “Functional testing of humoral immunity in the Prevnar 20 era.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2024). PMID: 39681261 ↗
L5REVIEW_NARRATIVECited in: Acute Management & Anaphylaxis Pathway, Prevention, Screening & Surveillance
[167]
Lang-Meli J, Fuchs J, Mathé P et al.. “Case Series: Convalescent Plasma Therapy for Patients with COVID-19 and Primary Antibody Deficiency.” Journal of clinical immunology (2021). PMID: 34893946 ↗
L4CASE_REPORTCited in: Acute Management & Anaphylaxis Pathway
[168]
Ilkjær FV, Johansen IS, Martin-Iguacel R et al.. “Evaluating Drug Prescription Patterns in Undiagnosed Common Variable Immunodeficiency Patients.” Journal of clinical immunology (2023). PMID: 37833619 ↗
L3OTHERCited in: Acute Management & Anaphylaxis Pathway
[169]
Ilkjær FV, Rasmussen LD, Martin-Iguacel R et al.. “How to Identify Common Variable Immunodeficiency Patients Earlier: General Practice Patterns.” Journal of clinical immunology (2019). PMID: 31372799 ↗
L3OTHERCited in: Acute Management & Anaphylaxis Pathway
[170]
Lawrence MG, Palacios-Kibler TV, Workman LJ et al.. “Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID).” Journal of clinical immunology (2018). PMID: 29453744 ↗
L3OTHERCited in: Acute Management & Anaphylaxis Pathway, Prevention, Screening & Surveillance
[171]
Baloh C, Reddy A, Henson M et al.. “30-Year Review of Pediatric- and Adult-Onset CVID: Clinical Correlates and Prognostic Indicators.” Journal of clinical immunology (2019). PMID: 31377970 ↗
L2REVIEW_NARRATIVECited in: Acute Management & Anaphylaxis Pathway, Special Populations & Pregnancy
[172]
Cagdas D, Halaçlı SO, Tan Ç et al.. “A Spectrum of Clinical Findings from ALPS to CVID: Several Novel LRBA Defects.” Journal of clinical immunology (2019). PMID: 31432443 ↗
L4OTHERCited in: Acute Management & Anaphylaxis Pathway
[173]
Steiner S, Schwarz T, Corman VM et al.. “Impaired B Cell Recall Memory and Reduced Antibody Avidity but Robust T Cell Response in CVID Patients After COVID-19 Vaccination.” Journal of clinical immunology (2023). PMID: 36932291 ↗
L4OTHERCited in: Acute Management & Anaphylaxis Pathway
[174]
Aiello V, Ferrillo M, Marotta N et al.. “Temporomandibular joint arthritis in rheumatic diseases patients: which are the effective rehabilitative approaches for pain relief? A systematic review.” BMC musculoskeletal disorders (2025). PMID: 39966784 ↗
L1SR_OBSCited in: Acute Management & Anaphylaxis Pathway
[175]
Budhipramono A, Sharma R, Wysocki CA et al.. “Therapeutic Plasma Exchange Management for a Pediatric Patient Presenting With Immune Thrombotic Thrombocytopenic Purpura in a Setting of Common Variable Immunodeficiency.” Journal of clinical apheresis (2024). PMID: 39511768 ↗
L4SR_OBSCited in: Acute Management & Anaphylaxis Pathway, Special Populations & Pregnancy
[176]
Napiórkowska-Baran K, Biliński J, Pujanek M et al.. “Fecal microbiota transplantation in a patient with chronic diarrhea and primary and secondary immunodeficiency (common variable immunodeficiency and splenectomy).” Frontiers in cellular and infection microbiology (2024). PMID: 39403201 ↗
L4CASE_REPORTCited in: Acute Management & Anaphylaxis Pathway
[177]
Bermingham WH, Canning B, Wilton T et al.. “Case report: Clearance of longstanding, immune-deficiency-associated, vaccine-derived polio virus infection following remdesivir therapy for chronic SARS-CoV-2 infection.” Frontiers in immunology (2023). PMID: 36936936 ↗
L4CASE_REPORTCited in: Acute Management & Anaphylaxis Pathway, Special Populations & Pregnancy
[178]
Martins B, Miranda J, Pinto MJ et al.. “Common variable immunodeficiency and its inflammatory neurological manifestations: A case report and literature review.” Multiple sclerosis and related disorders (2022). PMID: 35985210 ↗
L4CASE_REPORTCited in: Acute Management & Anaphylaxis Pathway, Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics
[179]
Luterbacher F, Bernard F, Baleydier F et al.. “Case Report: Persistent Hypogammaglobulinemia More Than 10 Years After Rituximab Given Post-HSCT.” Frontiers in immunology (2021). PMID: 35003091 ↗
L4CASE_REPORTCited in: Acute Management & Anaphylaxis Pathway, Special Populations & Pregnancy
[180]
Rezaei N, Hedayat M, Aghamohammadi A et al.. “Primary immunodeficiency diseases associated with increased susceptibility to viral infections and malignancies.” The Journal of allergy and clinical immunology (2011). PMID: 21514636 ↗
L5REVIEW_NARRATIVECited in: Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics, Prevention, Screening & Surveillance
[181]
Mazza JM, Lin SY. “Primary immunodeficiency and recalcitrant chronic sinusitis: a systematic review.” International forum of allergy & rhinology (2016). PMID: 27187624 ↗
L2SR_OBSCited in: Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics
[182]
Arslan S, Poyraz N, Ucar R et al.. “Magnetic Resonance Imaging May Be a Valuable Radiation-Free Technique for Lung Pathologies in Patients with Primary Immunodeficiency.” Journal of clinical immunology (2015). PMID: 26707785 ↗
L4OTHERCited in: Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics
[183]
Indinnimeo L, Tancredi G, Barreto M et al.. “Effects of a program of hospital-supervised chest physical therapy on lung function tests in children with chronic respiratory disease: 1-year follow-up.” International journal of immunopathology and pharmacology (2007). PMID: 18179758 ↗
L1RCTCited in: Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics
[184]
Pietzsch L, Körholz J, Boschann F et al.. “Hyper-IgE and Carcinoma in CADINS Disease.” Frontiers in immunology (2022). PMID: 35651609 ↗
L4CASE_REPORTCited in: Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics
[185]
Comberiati P, Costagliola G, Carli N et al.. “Refractory Chronic Spontaneous Urticaria Treated With Omalizumab in an Adolescent With Common Variable Immunodeficiency.” Frontiers in immunology (2019). PMID: 31379880 ↗
L4CASE_REPORTCited in: Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics
[186]
Suyama K, Kawasaki Y, Abe Y et al.. “Development of common variable immunodeficiency in IgA- and IgG2-deficient patients with systemic lupus erythematosus.” Pediatric nephrology (Berlin, Germany) (2011). PMID: 22207346 ↗
L4CASE_REPORTCited in: Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics
[187]
Zdziarski P, Gamian A. “Lymphoid Interstitial Pneumonia in Common Variable Immune Deficiency - Case Report With Disease Monitoring in Various Therapeutic Options: Pleiotropic Effects of Rituximab Regimens.” Frontiers in pharmacology (2019). PMID: 30713498 ↗
L4CASE_REPORTCited in: Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics
[188]
Yuan S, Hu X, Zhao Y et al.. “Case Report: PD-1 Inhibitor Is Active in Lung Adenocarcinoma With B Cell Deficiency.” Frontiers in immunology (2020). PMID: 33240259 ↗
L4CASE_REPORTCited in: Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics
[189]
Antachopoulos C, Walsh TJ, Roilides E. “Fungal infections in primary immunodeficiencies.” European journal of pediatrics (2007). PMID: 17551753 ↗
L5REVIEW_NARRATIVECited in: Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics
[190]
van Leeuwen LPM, GeurtsvanKessel CH, Ellerbroek PM et al.. “Immunogenicity of the mRNA-1273 COVID-19 vaccine in adult patients with inborn errors of immunity.” The Journal of allergy and clinical immunology (2022). PMID: 35421449 ↗
L2RCTCited in: Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Complications, Comorbidities & Iatrogenic Risks
[191]
Davé S, Hagan J. “Myocardial infarction during intravenous immunoglobulin infusion in a 65-year-old man with common variable immunodeficiency and subsequent successful repeated administration.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2007). PMID: 18219840 ↗
L4CASE_REPORTCited in: Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[192]
Morsheimer MM, Rychik J, Forbes L et al.. “Risk Factors and Clinical Significance of Lymphopenia in Survivors of the Fontan Procedure for Single-Ventricle Congenital Cardiac Disease.” The journal of allergy and clinical immunology. In practice (2016). PMID: 26897303 ↗
L2OTHERCited in: Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[193]
van Leeuwen LPM, Grobben M, GeurtsvanKessel CH et al.. “Immune Responses 6 Months After mRNA-1273 COVID-19 Vaccination and the Effect of a Third Vaccination in Patients with Inborn Errors of Immunity.” Journal of clinical immunology (2023). PMID: 37231290 ↗
L2OTHERCited in: Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[194]
Giardino G, Milito C, Lougaris V et al.. “The Impact of SARS-CoV-2 Infection in Patients with Inborn Errors of Immunity: the Experience of the Italian Primary Immunodeficiencies Network (IPINet).” Journal of clinical immunology (2022). PMID: 35445287 ↗
L4OTHERCited in: Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Special Populations & Pregnancy
[195]
Beyls E, Duthoo E, Backers L et al.. “Investigating Chromosomal Radiosensitivity in Inborn Errors of Immunity: Insights from DNA Repair Disorders and Beyond.” Journal of clinical immunology (2025). PMID: 39945898 ↗
L3OTHERCited in: Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution
[196]
Lin L, Peng X, Chen L et al.. “Case report: novel NFKB2 variant associated with pediatric eosinophilic granulomatosis with polyangiitis (EGPA) in the COVID-19 pandemic.” Pediatric rheumatology online journal (2025). PMID: 40165201 ↗
L4CASE_REPORTCited in: Immunodeficiency Management: Immunoglobulin Replacement, Prophylaxis and Immune Reconstitution, Special Populations & Pregnancy
[197]
Grammatikos A. “Enteropathy in Common Variable Immunodeficiency.” The journal of allergy and clinical immunology. In practice (2026). PMID: 41935739 ↗
L5REVIEW_NARRATIVECited in: Complications, Comorbidities & Iatrogenic Risks
[198]
Gregersen S, Aaløkken TM, Mynarek G et al.. “Development of pulmonary abnormalities in patients with common variable immunodeficiency: associations with clinical and immunologic factors.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (2010). PMID: 20568383 ↗
L2OTHERCited in: Complications, Comorbidities & Iatrogenic Risks, Prognosis & Natural History
[199]
Nguyen JT, Green A, Wilson MR et al.. “Neurologic Complications of Common Variable Immunodeficiency.” Journal of clinical immunology (2016). PMID: 27704236 ↗
L4CASE_REPORTCited in: Complications, Comorbidities & Iatrogenic Risks
[200]
Kralickova P, Kurecova B, Andrys C et al.. “Pregnancy Outcome in Patients with Common Variable Immunodeficiency.” Journal of clinical immunology (2015). PMID: 26280892 ↗
L2OTHERCited in: Complications, Comorbidities & Iatrogenic Risks, Prognosis & Natural History, Special Populations & Pregnancy
[201]
Zarezadeh Mehrabadi A, Aghamohamadi N, Abolhassani H et al.. “Comprehensive Assessment of Skin Disorders in Patients with Common Variable Immunodeficiency (CVID).” Journal of clinical immunology (2022). PMID: 35084691 ↗
L4OTHERCited in: Complications, Comorbidities & Iatrogenic Risks
[202]
Elmoursi A, Zhou B, Ong MS et al.. “A Cross-Sectional Study of Health-Related Quality of Life in Patients with Predominantly Antibody Deficiency.” Journal of clinical immunology (2024). PMID: 39110257 ↗
L2OTHERCited in: Complications, Comorbidities & Iatrogenic Risks, Prevention, Screening & Surveillance
[203]
Cinkavuk E, Akyazi N, Calik E et al.. “An ICF framework analysis of the CVID quality of life questionnaire.” Disability and rehabilitation (2026). PMID: 42080371 ↗
L5OTHERCited in: Complications, Comorbidities & Iatrogenic Risks
[204]
Hayes KM, Boldt K, Schnorr PJ et al.. “Heterozygous NFKB1 variant causes inflammatory dysregulation shaped by broader genetic context in common variable immunodeficiency.” JCI insight (2026). PMID: 41869721 ↗
L5OTHERCited in: Complications, Comorbidities & Iatrogenic Risks
[205]
Delplanque M, Galicier L, Oziol E et al.. “AA Amyloidosis Secondary to Primary Immune Deficiency: About 40 Cases Including 2 New French Cases and a Systematic Literature Review.” The journal of allergy and clinical immunology. In practice (2020). PMID: 33007500 ↗
L4SR_OBSCited in: Prognosis & Natural History
[206]
Kuehn HS, Gloude NJ, Dimmock D et al.. “Abnormal SCID Newborn Screening and Spontaneous Recovery Associated with a Novel Haploinsufficiency IKZF1 Mutation.” Journal of clinical immunology (2021). PMID: 33855675 ↗
L4TRIAL_NONRANDOMCited in: Prognosis & Natural History, Prevention, Screening & Surveillance
[207]
van Leeuwen LPM, Van Coillie S, Prévot J et al.. “Long-term effects of COVID-19 in patients with primary immunodeficiency: An IPOPI worldwide survey.” The Journal of allergy and clinical immunology (2025). PMID: 40316182 ↗
L4OTHERCited in: Prognosis & Natural History
[208]
Verbsky JW, Hintermeyer MK, Simpson PM et al.. “Rituximab and antimetabolite treatment of granulomatous and lymphocytic interstitial lung disease in common variable immunodeficiency.” The Journal of allergy and clinical immunology (2020). PMID: 32745555 ↗
L4OTHERCited in: Prognosis & Natural History
[209]
da Silva SP, Resnick E, Lucas M et al.. “Lymphoid proliferations of indeterminate malignant potential arising in adults with common variable immunodeficiency disorders: unusual case studies and immunohistological review in the light of possible causative events.” Journal of clinical immunology (2011). PMID: 21744182 ↗
L4CASE_REPORTCited in: Prognosis & Natural History
[210]
Kuehn HS, Nunes-Santos CJ, Rosenzweig SD. “IKAROS-Associated Diseases in 2020: Genotypes, Phenotypes, and Outcomes in Primary Immune Deficiency/Inborn Errors of Immunity.” Journal of clinical immunology (2021). PMID: 33392855 ↗
L5REVIEW_NARRATIVECited in: Prognosis & Natural History
[211]
Caka C, Cimen O, Kahyaoğlu P et al.. “Selective IgM deficiency: Follow-up and outcome.” Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology (2021). PMID: 33706406 ↗
L4OTHERCited in: Prognosis & Natural History, Special Populations & Pregnancy
[212]
Navale P, Zimmerman O, Wedner J et al.. “Gastrointestinal pathology in Good's syndrome, thinking beyond common variable immunodeficiency: a clinicopathological observation.” Virchows Archiv : an international journal of pathology (2025). PMID: 40140088 ↗
L4CASE_REPORTCited in: Prognosis & Natural History
[213]
Roosens W, Staels F, Van Loo S et al.. “Rituximab and improved nodular regenerative hyperplasia-associated non-cirrhotic liver disease in common variable immunodeficiency: a case report and literature study.” Frontiers in immunology (2023). PMID: 37795099 ↗
L4CASE_REPORTCited in: Prognosis & Natural History
[214]
Almejún MB, Campos BC, Patiño V et al.. “Noninfectious complications in patients with pediatric-onset common variable immunodeficiency correlated with defects in somatic hypermutation but not in class-switch recombination.” The Journal of allergy and clinical immunology (2016). PMID: 27713077 ↗
L4OTHERCited in: Special Populations & Pregnancy
[215]
Alsaati N, Penney C, Helbig I et al.. “A predictive model for identification of pediatric individuals with common variable immunodeficiency through electronic medical records.” The Journal of allergy and clinical immunology (2025). PMID: 40058414 ↗
L3OTHERCited in: Special Populations & Pregnancy
[216]
van de Ven AA, Compeer EB, Bloem AC et al.. “Defective calcium signaling and disrupted CD20-B-cell receptor dissociation in patients with common variable immunodeficiency disorders.” The Journal of allergy and clinical immunology (2011). PMID: 22130422 ↗
L3OTHERCited in: Special Populations & Pregnancy
[217]
Novice T, Kariminia A, Del Bel KL et al.. “A Germline Mutation in the C2 Domain of PLCγ2 Associated with Gain-of-Function Expands the Phenotype for PLCG2-Related Diseases.” Journal of clinical immunology (2019). PMID: 31853824 ↗
L4CASE_REPORTCited in: Special Populations & Pregnancy
[218]
Freer M, Bhatia R, Preece K et al.. “Dietary intakes and nutritional issues in inborn errors of immunity: a systematic review.” Frontiers in immunology (2024). PMID: 39399505 ↗
L2SR_OBSCited in: Special Populations & Pregnancy
[219]
Nijhof LN, van Brussel M, Pots EM et al.. “Severe Fatigue Is Common Among Pediatric Patients with Primary Immunodeficiency and Is Not Related to Disease Activity.” Journal of clinical immunology (2021). PMID: 33728554 ↗
L2OTHERCited in: Special Populations & Pregnancy
[220]
Sanchez LA, Maggadottir SM, Pantell MS et al.. “Two Sides of the Same Coin: Pediatric-Onset and Adult-Onset Common Variable Immune Deficiency.” Journal of clinical immunology (2017). PMID: 28755066 ↗
L2OTHERCited in: Special Populations & Pregnancy
[221]
Kinoshita H, Durkee-Shock J, Jensen-Wachspress M et al.. “Robust Antibody and T Cell Responses to SARS-CoV-2 in Patients with Antibody Deficiency.” Journal of clinical immunology (2021). PMID: 33983545 ↗
L3OTHERCited in: Special Populations & Pregnancy
[222]
Tanyildiz HG, Dincaslan H, Yavuz G et al.. “Lymphoma Secondary to Congenital and Acquired Immunodeficiency Syndromes at a Turkish Pediatric Oncology Center.” Journal of clinical immunology (2016). PMID: 27492260 ↗
L4OTHERCited in: Special Populations & Pregnancy
[223]
Quinti I, Soresina A, Spadaro G et al.. “Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency.” Journal of clinical immunology (2007). PMID: 17510807 ↗
L2OTHERCited in: Special Populations & Pregnancy
[224]
Phuong LK, Cheung A, Agrawal R et al.. “Inborn Errors of Immunity in Children With Invasive Pneumococcal Disease: A Multicenter Prospective Study.” The Pediatric infectious disease journal (2023). PMID: 37463351 ↗
L2COHORTCited in: Special Populations & Pregnancy
[225]
Adin-Cinar S, Gelmez MY, Akdeniz N et al.. “Functions of NK and iNKT cells in pediatric and adult CVID, ataxia telangiectasia and agammaglobulinemia patients.” Immunology letters (2021). PMID: 34599947 ↗
L3TRIAL_NONRANDOMCited in: Special Populations & Pregnancy
[226]
Grześk E, Kołtan S, Dąbrowska A et al.. “Case report: Cellular therapy for hydroa vacciniforme-like lymphoproliferative disorder in pediatric common variable immunodeficiency with chronic active Epstein-Barr virus infection.” Frontiers in immunology (2022). PMID: 35990691 ↗
L4CASE_REPORTCited in: Special Populations & Pregnancy
[227]
Mokrane L, Tahiat A, Taguemount S et al.. “Improving screening for antibody deficiency using calculated globulin and serum protein electrophoresis.” Frontiers in immunology (2026). PMID: 41929515 ↗
L4OTHERCited in: Special Populations & Pregnancy, Prevention, Screening & Surveillance
[228]
Lucas M, Lee M, Lortan J et al.. “Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years.” The Journal of allergy and clinical immunology (2010). PMID: 20471071 ↗
L2OTHERCited in: Prevention, Screening & Surveillance
[229]
Mayor PC, Eng KH, Singel KL et al.. “Cancer in primary immunodeficiency diseases: Cancer incidence in the United States Immune Deficiency Network Registry.” The Journal of allergy and clinical immunology (2017). PMID: 28606585 ↗
L2OTHERCited in: Prevention, Screening & Surveillance
[230]
Green PHR, Paski S, Ko CW et al.. “AGA Clinical Practice Update on Management of Refractory Celiac Disease: Expert Review.” Gastroenterology (2022). PMID: 36137844 ↗
L1GUIDELINECited in: Prevention, Screening & Surveillance
[231]
Israeli S, Golden A, Atalig M et al.. “A Novel Point-of-Care Rapid Diagnostic Test for Screening Individuals for Antibody Deficiencies.” Journal of clinical immunology (2021). PMID: 34839430 ↗
L4OTHERCited in: Prevention, Screening & Surveillance
[232]
Kermode W, De Santis D, Truong L et al.. “A Novel Targeted Amplicon Next-Generation Sequencing Gene Panel for the Diagnosis of Common Variable Immunodeficiency Has a High Diagnostic Yield: Results from the Perth CVID Cohort Study.” The Journal of molecular diagnostics : JMD (2022). PMID: 35570134 ↗
L4COHORTCited in: Prevention, Screening & Surveillance
[233]
Nassereddin AT, Zayed Y, King RB et al.. “A 28-Year-Old Woman With Nail Discoloration, Recurrent Bronchitis, and Left-Sided Facial Swelling.” Chest (2023). PMID: 37945195 ↗
L4CASE_REPORTCited in: Prevention, Screening & Surveillance
[234]
Camacho-Ordonez N, Hirsch A, Campos L et al.. “Do CVID patients on SCIG have more autoimmune (thrombo)cytopenic events than CVID patients on IVIG?” Frontiers in immunology (2025). PMID: 41394859 ↗
L2OTHERCited in: Prevention, Screening & Surveillance
[235]
Alba-Cano T, Alonso R, Balastegui-Martín H et al.. “Impact of CMV latency on T-cell responses to COVID-19 vaccination among predominantly antibody-deficient patients.” Frontiers in immunology (2025). PMID: 41098714 ↗
L2OTHERCited in: Prevention, Screening & Surveillance
[236]
Chandrasekaran P, Krausz M, Han Y et al.. “The intestinal microbiome and metabolome discern disease severity in cytotoxic T-lymphocyte-associated protein 4 deficiency.” Microbiome (2025). PMID: 39934899 ↗
L4Cited in: Pathophysiology & Immune Mechanism
[237]
Ortiz Requena D, Montgomery EA, Ronquillo NR et al.. “Multiple Myeloma and Mimicry: Gastrointestinal Tract Histologic Findings in Patients Following Chimeric Antigen Receptor T-cell Therapy and Anti-CD38 Monoclonal Antibodies.” Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (2026). PMID: 41864428 ↗
L4Cited in: Pathophysiology & Immune Mechanism
[238]
Tahiat A, Touri S, Saad-Djaballah A et al.. “Mapping the landscape of autoimmunity and autoinflammation in inborn errors of immunity: broad distribution with distinct clustering patterns.” Frontiers in immunology (2025). PMID: 41394846 ↗
L3bCited in: Pathophysiology & Immune Mechanism
[239]
Bez P, Santangeli E, Goldacker S et al.. “Expansion of CD57+ CD8 T cells in common variable immunodeficiency with hepatopathy and CMV infection.” Frontiers in immunology (2025). PMID: 40496855 ↗
L3bCited in: Pathophysiology & Immune Mechanism
[240]
Emmaneel A, Neirinck J, Torres-Valle A et al.. “PIDgeon: An Explainable AI Model for Improved Flow Cytometry-Based Screening of Lymphoid Primary Immunodeficiencies.” Clinical chemistry (2026). PMID: 41605242 ↗
L3bCited in: Pathophysiology & Immune Mechanism
[241]
Lopes da Silva VG, Schmitz GJH, Sullivan KE et al.. “Enhanced T-cell immunity and lower humoral responses following 5-dose SARS-CoV-2 vaccination in patients with inborn errors of immunity compared with healthy controls.” Frontiers in immunology (2025). PMID: 40114918 ↗
L4Cited in: Pathophysiology & Immune Mechanism
[242]
Felixberger PT, Andrieux G, Maul-Pavicic A et al.. “CD21low B cells reveal a unique glycosylation pattern with hypersialylation and hyperfucosylation.” Frontiers in immunology (2025). PMID: 40013136 ↗
L3bCited in: Pathophysiology & Immune Mechanism
[243]
Li M, Wang Q, Chen Y et al.. “Relieving the discrimination dilemma of adult autoimmune enteropathy and common variable immunodeficiency disease: two rare causes of chronic diarrhea and small intestinal villous atrophy.” Clinical rheumatology (2025). PMID: 40622608 ↗
L3bCited in: Pathophysiology & Immune Mechanism
[244]
Jogdand A, Gilbert KM, Hong JS et al.. “Utility of serum cytokine testing to differentiate complicated common variable immunodeficiency in resource limited settings.” The journal of allergy and clinical immunology. Global (2025). PMID: 40497017 ↗
L3bCited in: Pathophysiology & Immune Mechanism
[245]
Cousin V, Graumann A, Geiger V et al.. “Elevated IL-10 is Linked With the Expansion of T-bethighCD21low B Cells in Patients With Common Variable Immunodeficiency.” Journal of clinical immunology (2026). PMID: 42603226 ↗
L5Cited in: Pathophysiology & Immune Mechanism
[246]
Moriya K, Kamiyama Y, Ogino R et al.. “Clinical and immunological characterization of NFKB1 haploinsufficiency in Japan.” Frontiers in immunology (2026). PMID: 42488646 ↗
L5Cited in: Pathophysiology & Immune Mechanism
[247]
Moral Moral P, Cabanero-Navalon MD, López-León PT et al.. “Infectious outcomes of a standardized subcutaneous immunoglobulin dose reduction strategy in primary immune deficiencies amid global shortage.” Frontiers in immunology (2025). PMID: 39902048 ↗
L4Cited in: Epidemiology, Etiology & Risk Factors
[248]
Korkmaz P, Toprak İD, Hormet Igde M et al.. “Tuberculosis screening in adult patients with inborn errors of immunity: a single-center cohort study.” Frontiers in immunology (2026). PMID: 42568392 ↗
L4Cited in: Epidemiology, Etiology & Risk Factors
[249]
Dogru Y, Atschekzei F, Dogru D et al.. “Clinical and immunological differentiation of isolated IgG and combined IgG & IgM deficiencies from common variable immunodeficiency.” Frontiers in immunology (2026). PMID: 41869311 ↗
L3bCited in: Epidemiology, Etiology & Risk Factors
[250]
Mechernene B, Lehours P, Rivière E et al.. “Stool Screening for Campylobacter Species in Hypogammaglobulinemic Patients Receiving Immunoglobulin Therapy.” Journal of clinical immunology (2025). PMID: 41099909 ↗
L4Cited in: Epidemiology, Etiology & Risk Factors
[251]
Martínez Mercader S, Garcia-Bustos V, Moral Moral P et al.. “Exploring Multidimensional Risk Factors Associated with Local Adverse Reactions to Subcutaneous Immunoglobulin Therapy: Insights from a Nationwide Multicenter Study.” Biomedicines (2025). PMID: 40868242 ↗
L3bCited in: Epidemiology, Etiology & Risk Factors
[252]
Elamine A, Benhsaien I, Ailal F et al.. “Autoimmune manifestations in children with inborn errors of immunity in Morocco: A study from the national registry.” Journal of translational autoimmunity (2025). PMID: 40678816 ↗
L3bCited in: Epidemiology, Etiology & Risk Factors
[253]
Ameratunga R, Byrnes CA, Jordan A et al.. “Common Variable Immune Deficiency Disorders (CVID) in the Indigenous Māori of Aotearoa (New Zealand) Are Associated With a High Prevalence of Bronchiectasis and Complete IgA Deficiency.” Scandinavian journal of immunology (2025). PMID: 41267378 ↗
L4Cited in: Epidemiology, Etiology & Risk Factors
[254]
Moral Moral P, Garcia-Bustos V, Balastegui-Martin H et al.. “Real-world patterns of immunoglobulin replacement therapy for infection prevention in common variable immunodeficiency: a multicenter nationwide study.” Frontiers in immunology (2025). PMID: 40771807 ↗
L3bCited in: Clinical Presentation
[255]
Allaoui A, Moundir A, Benhsaien I et al.. “Clinical, immunological, and genetic landscape of common variable immunodeficiency in Morocco: a nationwide multicenter study.” Frontiers in immunology (2025). PMID: 40703516 ↗
L3bCited in: Clinical Presentation
[256]
Gerek ME, Colkesen F, Onalan T et al.. “Comparative analysis of demographic and clinical features in common variable immunodeficiency and selective immunoglobulin G deficiency.” Allergy and asthma proceedings (2025). PMID: 41152686 ↗
L4Cited in: Clinical Presentation
[257]
Danieli MG, Claudi I, Auria S et al.. “Allergic Diseases in Common Variable Immunodeficiency: A Prospective Cross-Sectional Study on Prevalence and Allergy Biomarkers of Clinical Phenotypes.” Scandinavian journal of immunology (2026). PMID: 41845886 ↗
L3bCited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[258]
Lawrence MG, Kim VHD, Orange JS et al.. “Shared Decision-Making and Health-Related Quality of Life in the Diagnosis and Management of Patients With Inborn Errors of Immunity.” The journal of allergy and clinical immunology. In practice (2026). PMID: 42447994 ↗
L5Cited in: Diagnosis & Immunodiagnostics: Allergy Testing and Immune-Function Workup
[259]
Milito C, Firinu D, Bez P et al.. “A beacon in the dark: COVID-19 course in CVID patients from two European countries: Different approaches, similar outcomes.” Frontiers in immunology (2023). PMID: 36845159 ↗
L2bCited in: Severity, Grading & Risk Stratification
[260]
Pulvirenti F, Giufrè M, Pentimalli TM et al.. “Oropharyngeal microbial ecosystem perturbations influence the risk for acute respiratory infections in common variable immunodeficiency.” Frontiers in immunology (2024). PMID: 38873612 ↗
L3bCited in: Severity, Grading & Risk Stratification
[261]
Daza-Cajigal V, Segura-Guerrero M, López-Cueto M et al.. “Clinical manifestations and approach to the management of patients with common variable immunodeficiency and liver disease.” Frontiers in immunology (2023). PMID: 37342345 ↗
L4Cited in: Severity, Grading & Risk Stratification
[262]
Pendse AA, Maule JG, Neff JL et al.. “Plasma cells are essentially absent in the luminal gastrointestinal tract of patients with "complete" 22q11.2 deletion syndrome (DiGeorge syndrome).” Human pathology (2021). PMID: 34391747 ↗
L3bCited in: Severity, Grading & Risk Stratification
[263]
Makary CA, Behnke J, Peppers B et al.. “Outcome of Immunoglobulin Replacement Therapy in Adults With Rhinosinusitis.” The Laryngoscope (2021). PMID: 34146351 ↗
L4Cited in: Severity, Grading & Risk Stratification
[264]
Bagkou Dimakou D, Peters NE, Burns SO et al.. “Serum sBCMA in primary and secondary antibody deficiency.” Clinical and experimental immunology (2025). PMID: 41017320 ↗
L3bCited in: Severity, Grading & Risk Stratification
[265]
Guerra-Galán T, Palacios-Ortega M, Jiménez-Huete A et al.. “An Exploratory Approach of Clinically Useful Biomarkers of Cvid by Logistic Regression.” Journal of clinical immunology (2024). PMID: 38847936 ↗
L3bCited in: Severity, Grading & Risk Stratification
[266]
Więsik-Szewczyk E, Rutkowska E, Kwiecień I et al.. “Patients with Common Variable Immunodeficiency Complicated by Autoimmune Phenomena Have Lymphopenia and Reduced Treg, Th17, and NK Cells.” Journal of clinical medicine (2021). PMID: 34362140 ↗
L4Cited in: Severity, Grading & Risk Stratification
[267]
van Leeuwen LPM, Grobben M, GeurtsvanKessel CH et al.. “Immunogenicity of COVID-19 booster vaccination in IEI patients and their one year clinical follow-up after start of the COVID-19 vaccination program.” Frontiers in immunology (2024). PMID: 38698851 ↗
L4Cited in: Acute Management & Anaphylaxis Pathway
[268]
Lin FJ, Doss AMA, Davis-Adams HG et al.. “SARS-CoV-2 booster vaccination rescues attenuated IgG1 memory B cell response in primary antibody deficiency patients.” Frontiers in immunology (2022). PMID: 36618402 ↗
L2bCited in: Acute Management & Anaphylaxis Pathway
[269]
Svačina MKR, Meißner A, Schweitzer F et al.. “Immunomodulatory effects of intravenous and subcutaneous immunoglobulin in chronic inflammatory demyelinating polyneuropathy: An observational study.” European journal of neurology (2023). PMID: 37789648 ↗
L4Cited in: Acute Management & Anaphylaxis Pathway
[270]
Cabañero-Navalon MD, Garcia-Bustos V, Nuñez-Beltran M et al.. “Current clinical spectrum of common variable immunodeficiency in Spain: The multicentric nationwide GTEM-SEMI-CVID registry.” Frontiers in immunology (2022). PMID: 36389743 ↗
L3bCited in: Acute Management & Anaphylaxis Pathway
[271]
La Civita E, Zannella C, Brusa S et al.. “BNT162b2 Elicited an Efficient Cell-Mediated Response against SARS-CoV-2 in Kidney Transplant Recipients and Common Variable Immunodeficiency Patients.” Viruses (2023). PMID: 37632002 ↗
L3bCited in: Acute Management & Anaphylaxis Pathway
[272]
Goda V, Kriván G, Kulcsár A et al.. “Specific Antibody and the T-Cell Response Elicited by BNT162b2 Boosting After Two ChAdOx1 nCoV-19 in Common Variable Immunodeficiency.” Frontiers in immunology (2022). PMID: 35784359 ↗
L3bCited in: Acute Management & Anaphylaxis Pathway
[273]
Sauerwein KMT, Geier CB, Stemberger RF et al.. “Antigen-Specific CD4+ T-Cell Activation in Primary Antibody Deficiency After BNT162b2 mRNA COVID-19 Vaccination.” Frontiers in immunology (2022). PMID: 35237272 ↗
L3bCited in: Acute Management & Anaphylaxis Pathway
[274]
Guevara-Hoyer K, Saz-Leal P, Diez-Rivero CM et al.. “Trained Immunity Based-Vaccines as a Prophylactic Strategy in Common Variable Immunodeficiency. A Proof of Concept Study.” Biomedicines (2020). PMID: 32660100 ↗
L3bCited in: Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics
[275]
Quartuccio L, De Marchi G, Longhino S et al.. “Shared Pathogenetic Features Between Common Variable Immunodeficiency and Sjögren's Syndrome: Clues for a Personalized Medicine.” Frontiers in immunology (2021). PMID: 34322134 ↗
L5Cited in: Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics
[276]
Cunningham-Rundles C. “How I treat common variable immune deficiency.” Blood (2010). PMID: 20332369 ↗
L5Cited in: Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics
[277]
Antachopoulos C. “Invasive fungal infections in congenital immunodeficiencies.” Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases (2010). PMID: 20840542 ↗
L5Cited in: Long-term & Definitive Management: Avoidance, Immunotherapy, Biologics
[278]
Danieli MG, Murdaca G, Mezzanotte C et al.. “Polyautoimmunity Reflecting Immune Dysregulation in Common Variable Immunodeficiency.” Biomedicines (2025). PMID: 40149529 ↗
L4Cited in: Complications, Comorbidities & Iatrogenic Risks
[279]
Martínez Mercader S, Garcia-Bustos V, Moral Moral P et al.. “Patient-centered outcomes with subcutaneous immunoglobulin use for infection control in primary and secondary immunodeficiencies: data of a GEIE Spanish Registry.” Frontiers in immunology (2025). PMID: 40028320 ↗
L3bCited in: Complications, Comorbidities & Iatrogenic Risks
[280]
Marri L, Contini P, Ivaldi F et al.. “Evaluation of Frequency of CMV Replication and Disease Complications Reveals New Cellular Defects and a Time Dependent Pattern in CVID Patients.” Journal of clinical immunology (2024). PMID: 38847943 ↗
L3bCited in: Prognosis & Natural History
[281]
Sadi Aykan F, Akın Saygın D, Çölkesen F et al.. “Brain Volume Alterations and Cognitive Functions in Patients with Common Variable Immunodeficiency: Evaluating the Impact of Autoimmunity.” Journal of clinical medicine (2026). PMID: 41598442 ↗
L3bCited in: Prognosis & Natural History
[282]
Cabañero-Navalon MD, Garcia-Bustos V, Balastegui-Martin H et al.. “The impact of immune dysregulation on the risk of malignancy in common variable immunodeficiency: insights from a multicenter study.” Frontiers in immunology (2024). PMID: 39478863 ↗
L3bCited in: Prognosis & Natural History
[283]
Correa-Jimenez O, Restrepo-Gualteros S, Nino G et al.. “Respiratory Comorbidities Associated with Bronchiectasis in Patients with Common Variable Immunodeficiency in the USIDNET Registry.” Journal of clinical immunology (2023). PMID: 37932514 ↗
L3bCited in: Prognosis & Natural History
[284]
Ciccarese F, Piva N, Carpano M et al.. “CT Features of Granulomatous-Lymphocytic Interstitial Lung Disease (GLILD): The "Kebab Sign" as a Marker to Support Differential Diagnosis.” Diagnostics (Basel, Switzerland) (2026). PMID: 42196862 ↗
L4Cited in: Prognosis & Natural History
[285]
King AL, Johnson EF, Alavi A et al.. “The Spectrum of Cutaneous Granulomatous Inflammation and Detection of Rubella Virus in Skin Biopsies of Patients With Common Variable Immune Deficiency.” Journal of cutaneous pathology (2024). PMID: 39588762 ↗
L4Cited in: Prognosis & Natural History
[286]
Pulvirenti F, Villa A, D'Ambrosi M et al.. “Changes in health-related quality of life in common variable immunodeficiency: an eight-year journey, including the COVID-19 pandemic.” Expert review of clinical immunology (2024). PMID: 38994591 ↗
L3bCited in: Prognosis & Natural History
[287]
Tessarin G, Baronio M, Gazzurelli L et al.. “Rituximab Monotherapy Is Effective as First-Line Treatment for Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) in CVID Patients.” Journal of clinical immunology (2023). PMID: 37755605 ↗
L4Cited in: Prognosis & Natural History
[288]
Bintalib HM, Raya RP, Alluhibi R et al.. “Utility of the 6-minute walk test and health-related quality of life questionnaires in granulomatous and lymphocytic interstitial lung disease.” Multidisciplinary respiratory medicine (2026). PMID: 42083912 ↗
L4Cited in: Prognosis & Natural History
[289]
Teräsjärvi J, Kainulainen L, Peltola V et al.. “Genetic polymorphisms of TLR1, TLR2, TLR3 and TLR4 in patients with recurrent or severe infections.” International journal of immunogenetics (2024). PMID: 38706134 ↗
L4Cited in: Prognosis & Natural History
[290]
Milito C, Pulvirenti F, Garzi G et al.. “Decline of gastric cancer mortality in common variable immunodeficiency in the years 2018-2022.” Frontiers in immunology (2023). PMID: 37868983 ↗
L4Cited in: Prevention, Screening & Surveillance
[291]
Bruns L, Panagiota V, von Hardenberg S et al.. “Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors.” Frontiers in immunology (2022). PMID: 35250968 ↗
L3bCited in: Prevention, Screening & Surveillance