Biomarkers of Lyme neuroborreliosis: a systematic review
- 1Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet Esther Møllers Vej 6, Copenhagen Ø, Denmark DK-2100
- 2Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Abstract
Background: The persistent challenges with diagnosing Lyme neuroborreliosis (LNB) have fostered investigations in a broad spectrum of biomarker candidates. The aim of this systematic review is to provide a comprehensive overview of these potential biomarkers of LNB.
Methods: We conducted a systematic literature review in accordance with PRISMA guidelines on Medline, Embase, Scopus, and Web of Science. The study protocol was published on PROSPERO prior to study-initiation. Studies identified through the combined search strings were screened for eligibility by independent physicians with expertise in LNB. Quality assessment and risk of bias was determined for all included studies using the QUADAS-2 assessment tool. In addition, criteria for consistency and a quality-score were established to quantify and compare diagnostic potential of biomarkers across studies.
Results: The search-strings yielded a total of 3113 unique studies of which 74 studies were found eligible for inclusion. The included studies investigated 220 different biomarkers in a total of 2598 patients with LNB from 1990 to 2025 in 13 different countries. No blood-based biomarkers showed consistent diagnostic potential across studies. IL-10 was ranked as the most promising biomarker in CSF.
Conclusion: The biomarker literature in LNB is characterized by substantial redundancy, with few candidates demonstrating consistent diagnostic potential across studies. Future research should prioritize rigorous validation of the most promising biomarkers rather than continued exploratory investigations to accelerate clinical translation.In addition, improved knowledge of LNB pathogenesis is a requisite for targeted biomarker discovery.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s15010-026-02875-y.
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BibTeX
@article{fjordside2026biomarkers,
title = {{Biomarkers of Lyme neuroborreliosis: a systematic review}},
author = {Lasse Fjordside and Anna Maria Florescu and Al-Hasan Hussein Dos and Mathilde Ørbaek and Helene Mens and Anne-Mette Lebech},
journal = {Infection},
year = {2026},
month = aug,
doi = {10.1007/s15010-026-02875-y},
url = {https://doi.org/10.1007/s15010-026-02875-y},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Biomarkers of Lyme neuroborreliosis: a systematic review
AU - Lasse Fjordside
AU - Anna Maria Florescu
AU - Al-Hasan Hussein Dos
AU - Mathilde Ørbaek
AU - Helene Mens
AU - Anne-Mette Lebech
PY - 2026
DA - 2026/08/03
JO - Infection
DO - 10.1007/s15010-026-02875-y
UR - https://doi.org/10.1007/s15010-026-02875-y
AB - Background: The persistent challenges with diagnosing Lyme neuroborreliosis (LNB) have fostered investigations in a broad spectrum of biomarker candidates. The aim of this systematic review is to provide a comprehensive overview of these potential biomarkers of LNB. Methods: We conducted a systematic literature review in accordance with PRISMA guidelines on Medline, Embase, Scopus, and Web of Science. The study protocol was published on PROSPERO prior to study-initiation. Studies identified through the combined search strings were screened for eligibility by independent physicians with expertise in LNB. Quality assessment and risk of bias was determined for all included studies using the QUADAS-2 assessment tool. In addition, criteria for consistency and a quality-score were established to quantify and compare diagnostic potential of biomarkers across studies. Results: The search-strings yielded a total of 3113 unique studies of which 74 studies were found eligible for inclusion. The included studies investigated 220 different biomarkers in a total of 2598 patients with LNB from 1990 to 2025 in 13 different countries. No blood-based biomarkers showed consistent diagnostic potential across studies. IL-10 was ranked as the most promising biomarker in CSF. Conclusion: The biomarker literature in LNB is characterized by substantial redundancy, with few candidates demonstrating consistent diagnostic potential across studies. Future research should prioritize rigorous validation of the most promising biomarkers rather than continued exploratory investigations to accelerate clinical translation.In addition, improved knowledge of LNB pathogenesis is a requisite for targeted biomarker discovery. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s15010-026-02875-y.
SN - 0300-8126
SN - 1439-0973
ER -