Association of antibiotic treatment-resistant lyme arthritis with T cell responses to dominant epitopes of outer surface protein A of Borrelia burgdorferi

Objective. To explore further the association of antibiotic treatment-resis tant Lyme arthritis and T cell reactivity with outer surface protein A (Osp A) of Borrelia burgdorferi, including the identification of T cell epitopes associated with this treatment-resistant course. Methods. The responses of peripheral blood and, if available, synovial flui d lymphocytes to B burgdorferi proteins, fragments, and synthetic peptides, as determined by proliferation assay and interferon-gamma production, were compared in 16 patients with treatment-responsive and 16 with treatment-re sistant Lyme arthritis. Results. The maximum severity of joint swelling correlated directly with th e response to OspA. Moreover, the only significant difference between patie nts with treatment-resistant and treatment-responsive arthritis was in reac tivity with N-terminal and C-terminal fragments of OspA, OspA1 (amino acids [aa] 16-106), and OspA3 (aa 168-273). Epitope mapping showed that 14 of th e 16 patients with treatment-resistant arthritis had responses to OspA pept ides (usually 4 or 5 epitopes), whereas only 5 of the 16 patients with trea tment-responsive arthritis had reactivity with these peptides (usually 1 or 2 epitopes) (P = 0.003). Patients with HLA-DRB1 alleles associated with tr eatment-resistant arthritis were more likely to react with peptide 15 (aa 1 54-173) and, to a lesser degree, with peptide 21 (aa 214-233) than patients with other alleles, whereas the responses to other epitopes were similar i n both groups. Conclusion. The maximum severity of joint swelling and the duration of Lyme arthritis after antibiotic treatment are associated with T cell responses to specific epitopes of OspA.