Binding of outer surface protein A and human lymphocyte function-associated antigen 1 peptides to HLA-DR molecules associated with antibiotic treatment-resistant Lyme arthritis

2003 ◽  
Vol 48 (2) ◽  
pp. 534-540 ◽  
Author(s):  
Allen C. Steere ◽  
Ben Falk ◽  
Elise E. Drouin ◽  
Lee Ann Baxter-Lowe ◽  
Juergen Hammer ◽  
...  
Keyword(s):  
Antibiotic Treatment ◽  
Human Lymphocyte ◽  
Outer Surface ◽  
Protein A ◽  
Surface Protein ◽  
Lyme Arthritis ◽  
Lymphocyte Function ◽  
Treatment Resistant ◽  
Outer Surface Protein A ◽  
Hla Dr

scholarly journals Occurrence of Severe Destructive Lyme Arthritis in Hamsters Vaccinated with Outer Surface Protein A and Challenged with Borrelia burgdorferi

2000 ◽  
Vol 68 (2) ◽  
pp. 658-663 ◽  
Author(s):  
Cindy L. Croke ◽  
Erik L. Munson ◽  
Steven D. Lovrich ◽  
John A. Christopherson ◽  
Monica C. Remington ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Aluminum Hydroxide ◽  
Outer Surface ◽  
Protein A ◽  
Surface Protein ◽  
Major Complication ◽  
Sensu Stricto ◽  
Lyme Arthritis ◽  
Outer Surface Protein A ◽  
Outer Surface Protein

ABSTRACT Arthritis is a frequent and major complication of infection withBorrelia burgdorferi sensu stricto. The antigens responsible for the induction of arthritis are unknown. Here we provide direct evidence that a major surface protein, outer surface protein A (OspA), can induce arthritis. Hamsters were vaccinated with 30, 60, or 120 μg of recombinant OspA (rOspA) in aluminum hydroxide and challenged with B. burgdorferi sensu stricto isolate 297 or C-1-11. Swelling of the hind paws was detected in 100, 100, and 50% of hamsters vaccinated with 30, 60, or 120 μg of rOspA, respectively. In addition, arthritis developed in 57% of hamsters vaccinated with a canine rOspA vaccine after infection with B. burgdorferisensu stricto. When the canine rOspA vaccine was combined with aluminum hydroxide, all vaccinated hamsters developed arthritis after challenge with B. burgdorferi sensu stricto. Histopathologic examination confirmed the development of severe destructive arthritis in rOspA-vaccinated hamsters challenged with B. burgdorferisensu stricto. These findings suggest that rOspA vaccines should be modified to eliminate epitopes of OspA responsible for the induction of arthritis. Our results are important because an rOspA vaccine in aluminum hydroxide was approved by the Food and Drug Administration for use in humans.

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

2006 ◽  
Vol 203 (4) ◽  
pp. 961-971 ◽  
Author(s):  
Allen C. Steere ◽  
William Klitz ◽  
Elise E. Drouin ◽  
Ben A. Falk ◽  
William W. Kwok ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Protein A ◽  
Surface Protein ◽  
Lyme Arthritis ◽  
Exact Test ◽  
Outer Surface Protein A ◽  
Leukocyte Antigen ◽  
Hla Dr ◽  
Antibiotic Response

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.

Sign in / Sign up

Export Citation Format

Share Document