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

• Published in: The Journal of experimental medicine Vol. 203; no. 4; pp. 961 - 971
• Main Authors: Steere, Allen C, Klitz, William, Drouin, Elise E, Falk, Ben A, Kwok, William W, Nepom, Gerald T, Baxter-Lowe, Lee Ann
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 17.04.2006
• Subjects: Adolescent; Adult; Aged; Anti-Bacterial Agents - pharmacology; Antigens, Surface - immunology; Antigens, Surface - metabolism; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Bacterial Outer Membrane Proteins - immunology; Bacterial Outer Membrane Proteins - metabolism; Bacterial Vaccines; Borrelia burgdorferi; Borrelia burgdorferi - immunology; Borrelia burgdorferi - metabolism; Child; Drug Resistance, Bacterial - genetics; Gene Frequency; Haplotypes; HLA-DR Antigens - genetics; HLA-DR Antigens - metabolism; HLA-DRB1 Chains; Humans; Lipoproteins - immunology; Lipoproteins - metabolism; Lyme Disease - drug therapy; Lyme Disease - genetics; Lyme Disease - immunology; Middle Aged; Peptide Fragments - immunology; Peptide Fragments - metabolism; Protein Binding
• ISSN: 0022-1007; 1540-9538; 1892-1007
• DOI: 10.1084/jem.20052471

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 (OspA163-175). 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 OspA163-175 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 OspA163-175, 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.