The Journal of Experimental Medicine
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Published online 3 April 2006 doi:10.1084/jem.20052471
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 4, 961-971
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*Lyme Disease
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ARTICLE

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

Allen C. Steere1, William Klitz2,3, Elise E. Drouin1, Ben A. Falk4, William W. Kwok4, Gerald T. Nepom4, and Lee Ann Baxter-Lowe5

1 Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114
2 University of California, Berkeley, and 3 Public Health Research Institute, Oakland, CA 94720
4 Benaroya Research Institute, Virginia Mason Medical Center, University of Washington, Seattle, WA 98101
5 Immunogenetics and Transplantation Laboratory, University of California, San Francisco, San Francisco, CA 94143

CORRESPONDENCE Allen C. Steere: asteere{at}partners.org

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.

Abbreviations used: CI, confidence interval; OR, odds ratio; OspA, outer-surface protein A; RA, rheumatoid arthritis.


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