Abstract
While most patients fully recover after treatment for Lyme disease with recommended antibiotic regimens, some report non-specific symptoms after treatment. When these symptoms are unexplained by other conditions and persist for ≥ 6 months, this condition is called post-treatment Lyme disease symptoms or syndrome (PTLDS). The pathogenesis of PTLDS is unknown and no specific diagnostic biomarkers have been identified. In this study, we used a high-density peptide array to examine antibody responses to > 60 primary antigens of B. burgdorferi from a cohort of patients diagnosed with PTLDS and recovered patients with similar Lyme disease manifestations. Using matched serum and cerebrospinal fluid (CSF), we mapped the primary reactive B. burgdorferi epitopes associated with PTLDS. We found that VlsE had a greater antibody response within the PTLDS cohort than recovered patients. The reactivity to OspC-specific epitopes revealed a predominance of antibodies to OspC type K and A in the PTLDS cohort. However, the major immunodominant epitopes were similar in PTLDS and recovered patients, and we were unable to identify specific diagnostic targets for PTLDS. We found a more robust reactivity in the serum over CSF and did not identify antigenic regions that were specifically associated with the infection of the central nervous system.
Data availability
All data generated in this study was deposited in Dryad, accessible under the following link: DOI: https://doi.org/10.5061/dryad.wpzgmsc1f.
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Acknowledgements
We would like to thank Cheng Guo and Teresa Tagliafierro for their contributions.
Funding
This study was funded by grants from the Global Lyme Alliance, The Steven & Alexandra Cohen Foundation, and the R01AI182237 (Tokarz). This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH). The contributions of the NIH author(s) are considered Works of the United States Government. The findings and conclusions presented in this paper are those of the author(s) and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services.
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ARM and RT designed the study and wrote the manuscript. AN performed the bioinformatics analyses. SSV assisted with data analysis and manuscript preparation. AE and SPN assisted with sample procurement. WIL provided intellectual input.
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Dr. Marques has a patent US 8,926,989 issued; and is an unpaid Scientific Advisor to the Global Lyme Alliance and to the American Lyme Disease Foundation.
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Marques, A.R., Sanchez-Vicente, S., Nagapurkar, A. et al. Evaluation of immunoreactive epitopes in the sera and cerebrospinal fluid of patients with post-treatment Lyme disease syndrome. Sci Rep (2026). https://doi.org/10.1038/s41598-026-42941-x
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DOI: https://doi.org/10.1038/s41598-026-42941-x