Identification of potential biomarkers in active Lyme borreliosis

PLoS One. 2023 Jun 26;18(6):e0287586. doi: 10.1371/journal.pone.0287586. eCollection 2023.


Objectives: Lyme serology does not readily discriminate an active Lyme borreliosis (LB) from a previous Borrelia infection or exposure. Here, we aimed to investigate a large number of immunological protein biomarkers to search for an immunological pattern typical for active LB, in contrast to patterns found in healthy blood donors, a proportion of whom were previously exposed to Borrelia.

Methods: Serum samples from well-characterised adult patients with ongoing LB and healthy blood donors were included and investigated using a proximity extension assay (provided by Olink®) by which 92 different immune response-related human protein biomarkers were analysed simultaneously.

Results: In total, 52 LB patients and 75 healthy blood donors were included. The blood donors represented both previously Borrelia exposed (n = 34) and not exposed (n = 41) based on anti-Borrelia antibody status. Ten of the examined 92 proteins differed between patients and blood donors and were chosen for further logistic regression (p<0.1). Six proteins were statistically significantly different between LB patients and blood donors (p<0.05). These six proteins were then combined in an index and analysed using receiver-operating-characteristic curve analysis showing an area under the curve of 0.964 (p<0.001).

Conclusions: The results from this study suggest that there is an immunological protein pattern that can distinguish a present Borrelia infection from a previous exposure as well as anti-Borrelia antibody negative blood donors. Although this method is not adapted for routine clinical use at this point, the possibility is interesting and may open new diagnostic opportunities improving the laboratory diagnostics of LB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Bacterial
  • Biomarkers
  • Blood Donors
  • Borrelia burgdorferi*
  • Borrelia*
  • Clinical Laboratory Techniques
  • Humans
  • Lyme Disease* / diagnosis


  • Biomarkers
  • Antibodies, Bacterial

Grants and funding

This study was supported by university grants to Region Kalmar County (IT), Futurum-Academy for Healthcare and Division of Medical Diagnostics, Region Jönköping County, Interreg IVA Program ScandTick (grant no. 167226) and Interreg V program ScandTick Innovation (project ID. 20200422, reference no. 2015-29 000167), The Medical Research Council of Southeast Sweden (FORSS-475511), the foundation for medical research of the Åland cultural foundation and the Wilhelm and Else Stockmann Foundation (AJH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.