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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-42941-x.