Serum Borrelia IgG as a rule-out test in suspected lyme neuroborreliosis: a large retrospective cohort study
In brief
After two weeks, negative serum Lyme IgG had 99% negative predictive value
In this retrospective Danish cohort, a negative serum Lyme antibody result after at least two weeks of symptoms was associated with a 99% chance that patients did not have neuroborreliosis; after four weeks, negative predictive value reached 100%. The test could help guide decisions about lumbar puncture, but the findings come from a selected cohort and need prospective external validation.
- Journal
- European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology (Q1)
- Published
- 2 October 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Al-Hasan Hussein Dos, Anne-Mette Lebech, Jonas Bredtoft Boel, Lene Nielsen, Helene Mens, Masoud Moradi, et al.
- PMID
- 42825978
- DOI
- 10.1007/s10096-026-05679-y
Why clinicians should know about it
- Picked for Microbiology (medical) (paper of the day, 4 October 2026): Serum IgG rule‑out test for neuroborreliosis
Abstract
OBJECTIVES: In Europe, the diagnosis of Lyme neuroborreliosis (NB) relies on intrathecal Borrelia burgdorferi sensu lato (Bbsl) antibody production, but this test has limited sensitivity in early disease and requires lumbar puncture (LP). We therefore evaluated the diagnostic performance of the quantitative LIAISON® serum Bbsl IgG assay across clinically relevant subgroups and its potential to guide LP decisions in patients with suspected NB. METHODS: We retrospectively analyzed 3,841 patients who underwent intrathecal Bbsl antibody testing in the Capital Region of Denmark (2016-2024). NB cases were defined by European criteria and matched to non-NB controls. We assessed sensitivity, specificity, predictive values, area under the curve (AUC), and accuracy of Bbsl IgG across age groups, symptom durations, and clinical scenarios, and used logistic regression to model NB probability from serum IgG titers. RESULTS: We included 392 NB patients and 2,681 non-NB controls, all with available serum Bbsl IgG LIAISON® results. Overall sensitivity and specificity were both 88%. Accuracy was highest in children (0.90), while AUC peaked in patients with symptom duration > 4 weeks (0.96). Among patients with symptoms ≥ 2 weeks, sensitivity was 98% and negative predictive value 99%. For those with > 4 weeks symptom duration, both reached 100%. Predicted NB probability increased progressively with higher serum Bbsl titers. INTERPRETATION: Taken together, our findings support a re-evaluation of the diagnostic sequence in suspected NB, although prospective external validation is required. A negative quantitative VlsE-based serum Bbsl IgG result after ≥ 2 weeks of symptoms was associated with a very low probability of NB in this selected cohort, supporting its potential use as a rule-out tool to guide LP decisions.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.