To explore further the association of antibiotic treatment–resistant Lyme arthritis and T cell reactivity with outer surface protein A (OspA) of Borrelia burgdorferi, including the identification of T cell epitopes associated with this treatment‐resistant course.

The responses of peripheral blood and, if available, synovial fluid lymphocytes to B burgdorferi proteins, fragments, and synthetic peptides, as determined by proliferation assay and interferon‐γ production, were compared in 16 patients with treatment‐responsive and 16 with treatment‐resistant Lyme arthritis.

The maximum severity of joint swelling correlated directly with the response to OspA. Moreover, the only significant difference between patients with treatment‐resistant and treatment‐responsive arthritis was in reactivity 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 the 16 patients with treatment‐resistant arthritis had responses to OspA peptides (usually 4 or 5 epitopes), whereas only 5 of the 16 patients with treatment‐responsive arthritis had reactivity with these peptides (usually 1 or 2 epitopes) (P = 0.003). Patients with HLA–DRB1 alleles associated with treatment‐resistant arthritis were more likely to react with peptide 15 (aa 154–173) and, to a lesser degree, with peptide 21 (aa 214–233) than patients with other alleles, whereas the responses to other epitopes were similar in both groups.

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.