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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>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.</p>

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Biomarkers of Lyme neuroborreliosis: a systematic review

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月3日

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  • Lasse Fjordside,
  • Anna Florescu,
  • Al-Hasan Hussein Dos,
  • Mathilde Ørbaek,
  • Helene Mens,
  • Anne-Mette Lebech

摘要

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.