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 (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.
Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. asteere@partners.org
Allen C
AC
Steere
William
W
Klitz
Elise E
EE
Drouin
Ben A
BA
Falk
William W
WW
Kwok
Gerald T
GT
Nepom
Lee Ann
LA
Baxter-Lowe
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D001428:Bacterial Vaccines; D025065:Borrelia burgdorferi / Q000276:immunology / Q000378:metabolism*; D002648:Child; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005787:Gene Frequency; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D008074:Lipoproteins / Q000276:immunology / Q000378:metabolism*; D008193:Lyme Disease / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding
D000900:Anti-Bacterial Agents; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; C553506:HLA-DRB1*04:02 antigen; D008074:Lipoproteins; C072045:OspA protein; D010446:Peptide Fragments