Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide

An association has previously been shown between antibiotic-refractory Lyme arthritis, the human histocompatibility leukocyte antigen (HLA)-DR4 molecule, and T cell recognition of an epitope of Borrelia burgdorferi outer-surface protein A (OspA(163-175)). We studied the frequencies of HLA-DRB1-DQA1-DQB1 haplotypes in 121 patients with antibiotic-refractory or antibiotic-responsive Lyme arthritis and correlated these frequencies with in vitro binding of the OspA(163-175) peptide to 14 DRB molecules. Among the 121 patients, the frequencies of HLA-DRB1-DQA1-DQB1 haplotypes were similar to those in control subjects. However, when stratified by antibiotic response, the frequencies of DRB1 alleles in the 71 patients with antibiotic- refractory arthritis differed significantly from those in the 50 antibiotic- responsive patients ( log likelihood test, P = 0.006; exact test, P = 0.008; effect size, Wn = 0.38). 7 of the 14 DRB molecules (DRB1*0401, 0101, 0404, 0405, DRB5*0101, DRB1*0402, and 0102) showed strong to weak binding of OspA(163-175), whereas the other seven showed negligible or no binding of the peptide. Altogether, 79% of the antibiotic- refractory patients had at least one of the seven known OspA peptide-binding DR molecules compared with 46% of the antibiotic- responsive patients (odds ratio = 4.4; P < 0.001). We conclude that binding of a single spirochetal peptide to certain DRB molecules is a marker for antibiotic- refractory Lyme arthritis and might play a role in the pathogenesis of the disease.