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

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Published online 3 April 2006 doi:10.1084/jem.20052471

© Rockefeller University Press, 0022-1007

JEM, Volume 203, Number 4, 961-971

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ARTICLE

Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules

that bind a Borrelia burgdorferi peptide

C. Steere1, Klitz2,3, Elise E. Drouin1, Ben A. Falk4,

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 C. Steere: asteere@...

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.

Full text of the article here:

http://www.jem.org/cgi/content/full/203/4/961

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