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.

scholarly journals Borrelia burgdorferi Escape Mutants That Survive in the Presence of Antiserum to the OspA Vaccine Are Killed When Complement Is Also Present

1998 ◽  
Vol 66 (6) ◽  
pp. 2540-2546 ◽  
Author(s):  
Mónica Solé ◽  
Carlos Bantar ◽  
Karl Indest ◽  
Yan Gu ◽  
Ramesh Ramamoorthy ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Protein A ◽  
Surface Protein ◽  
Sensu Stricto ◽  
Antibody Concentration ◽  
Initial Attempt ◽  
Outer Surface Protein A ◽  
Escape Mutants ◽  
Low Passage

ABSTRACT As an initial attempt to investigate the possible role of outer surface protein A (OspA) escape mutants of Borrelia burgdorferi in decreasing the efficacy of the OspA vaccine, mutants of the HB19 strain of B. burgdorferi sensu stricto were selected in vitro from an uncloned, low-passage-number isolate. The antiserum used for selection was obtained from rhesus monkeys that had been given a vaccine of the same formulation and dose, and by the same route of administration, as that given to humans in several trials. All of the mutants selected in liquid medium and subsequently cloned twice in solid medium expressed a single abundant protein of 28 to 34 kDa instead of both OspA and OspB. Depending on the mutant, this protein reacted strongly, weakly, or not detectably with the anti-OspA antibody used for selection. Analysis of the ospAB locus of each of four representatives from these three groups of mutants by PCR with oligonucleotide primers that hybridize to flanking regions of theospAB operon, and of the corresponding phenotype with monoclonal antibodies that bind to the amino or carboxyl terminus of the OspA or OspB polypeptide, indicated that in all cases a deletion within the operon had occurred. Spirochetes from the four mutant strains chosen for further analysis could be killed in antibody-dependent, complement-mediated killing assays with the selecting anti-OspA antibody, despite their resistance to killing with this antibody in the absence of complement. Complement-mediated killing occurred at an antibody concentration higher than that required to kill wild-type spirochetes. If anti-OspA antibody acts only within the tick, where complement is probably ineffective due to tick-derived decomplementing factors, then OspA escape mutants, if infectious, could seriously diminish the efficacy of OspA vaccines. On the other hand, if the killing of B. burgdorferi with anti-OspA antibody also takes place within the human host, then our results indicate that chimeric/deletion escape mutants will be killed as well.

scholarly journals Temporal Changes in Outer Surface Proteins A and C of the Lyme Disease-Associated Spirochete, Borrelia burgdorferi, during the Chain of Infection in Ticks and Mice

2000 ◽  
Vol 38 (1) ◽  
pp. 382-388 ◽  
Author(s):  
Tom G. Schwan ◽  
Joseph Piesman
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Outer Surface ◽  
Ixodes Scapularis ◽  
Protein A ◽  
Surface Protein ◽  
Surface Proteins ◽  
In Vitro Cultivation ◽  
Outer Surface Protein A

ABSTRACT The Lyme disease-associated spirochete, Borrelia burgdorferi, is maintained in enzootic cycles involvingIxodes ticks and small mammals. Previous studies demonstrated that B. burgdorferi expresses outer surface protein A (OspA) but not OspC when residing in the midgut of unfed ticks. However, after ticks feed on blood, some spirochetes stop making OspA and express OspC. Our current work examined the timing and frequency of OspA and OspC expression by B. burgdorferi in infected Ixodes scapularis nymphs as they fed on uninfected mice and in uninfected I. scapularis larvae and nymphs as they first acquired spirochetes from infected mice. Smears of midguts from previously infected ticks were prepared at 12- or 24-h intervals following attachment through repletion at 96 h, and spirochetes were stained for immunofluorescence for detection of antibodies to OspA and OspC. As shown previously, prior to feeding spirochetes in nymphs expressed OspA but not OspC. During nymphal feeding, however, the proportion of spirochetes expressing OspA decreased, while spirochetes expressing OspC became detectable. In fact, spirochetes rapidly began to express OspC, with the greatest proportion of spirochetes having this protein at 48 h of attachment and then with the proportion decreasing significantly by the time that the ticks had completed feeding. In vitro cultivation of the spirochete at different temperatures showed OspC to be most abundant when the spirochetes were grown at 37°C. Yet, the synthesis of this protein waned with continuous passage at this temperature. Immunofluorescence staining of spirochetes in smears of midguts from larvae and nymphs still attached or having completed feeding on infected mice demonstrated that OspA but not OspC was produced by these spirochetes recently acquired from mice. Therefore, the temporal synthesis of OspC by spirochetes only in feeding ticks that were infected prior to the blood meal suggests that this surface protein is involved in transmission from tick to mammal but not from mammal to tick.

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 Serum Reactivity against Borrelia burgdorferi OspA in Patients with Rheumatoid Arthritis

2007 ◽  
Vol 14 (11) ◽  
pp. 1437-1441 ◽  
Author(s):  
Yu-Fan Hsieh ◽  
Han-Wen Liu ◽  
Tsai-Ching Hsu ◽  
James C.-C. Wei ◽  
Chien-Ming Shih ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Healthy Subjects ◽  
Disease Activity Score ◽  
Protein A ◽  
Surface Protein ◽  
Lyme Arthritis ◽  
Serum Concentrations ◽  
Outer Surface Protein A

ABSTRACT Lyme arthritis and rheumatoid arthritis share common clinical features and synovial histology. It is unclear whether they also share similar pathogenesis. Previous studies have shown that the severity and duration of Lyme arthritis correlate directly with serum concentrations of antibody against outer surface protein A (OspA) of the causative pathogen Borrelia burgdorferi. We tested the sera of 68 subjects with rheumatoid arthritis, 147 subjects with other autoimmune diseases, and 44 healthy subjects who had never had Lyme disease, as well as sera of 16 patients who had Lyme disease, for reactivity against the B. burgdorferi OspA protein. The sera of about a quarter of the rheumatoid arthritis patients and a 10th of the autoimmune disease and Lyme disease patients reacted against OspA antigen. Of 50 rheumatoid arthritis patients who could be evaluated for disease severity, a 28-joint count disease activity score of >2.6 was noted for 11 of 15 (73%) patients whose sera reacted against OspA antigen and 13 of 35 (37%; P < 0.05) whose sera were nonreactive. Serum reactivity against OspA antigen is associated with the pathogenesis of rheumatoid arthritis.

Multiple cross-reactive seif-ligands for Borrelia burgdorferi outer surface protein A (OspA)-specific HLA-DR4-restricted T Cells

1999 ◽  
Vol 289 (5-7) ◽  
pp. 673 ◽  
Author(s):  
Bert Maier ◽  
Marc Molinger ◽  
Andrew P. Cope ◽  
Lars Fugger ◽  
Jens Schneider-Mergener ◽  
...  
Keyword(s):  
T Cells ◽  
Borrelia Burgdorferi ◽  
Outer Surface ◽  
Protein A ◽  
Surface Protein ◽  
Outer Surface Protein A ◽  
Outer Surface Protein ◽  
Multiple Cross
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