Reaction of anti-HLA-B monoclonal antibodies with envelope proteins of Shigella species. Evidence for molecular mimicry in the spondyloarthropathies.
Immunologic cross-reactivity between enteric bacteria and the HLA-B27 protein may play a role in the etiology of Reiter's syndrome and reactive arthritis. The reactivity of two anti-B27 mAb (B27M1 and B27M2) with envelope proteins of Shigella flexneri isolated from Reiter's syndrome patients was studied by Western blot analysis. Proteins with an apparent Mr of approximately 36 and 23 kDa reacted with both mAb in ascites. mAb against related HLA class I Ag B7 and B40 did not react with the 23 kDa protein. Relatively high concentrations of antibody were required for reactivity, suggesting a low affinity interaction. Additional evidence for cross-reactive epitopes was obtained by ELISA against whole envelope and by using unsolubilized envelope to inhibit binding of M1 and M2 to B27-positive cell lines, as measured by quantitative flow microfluorimetry. The presence of cross-reactive proteins was not related to the presence of the intact virulence-associated plasmid or the invasive phenotype. Two Shigella sonnei isolates not implicated as causative agents of Reiter's syndrome or reactive arthritis showed a similar pattern of cross-reactivity. These results indicate that cross-reactive epitopes may be present on "arthritogenic" bacteria, but their presence is not a unique feature of such strains and is not the sole factor in induction of arthritis in B27-positive individuals.
Raybourne
R B
RB
Division of Microbiology, Food and Drug Administration, Washington, DC 20204.
Bunning
V K
VK
Williams
K M
KM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis*; D000942:Antigens, Bacterial / Q000032:analysis / Q000276:immunology; D001168:Arthritis / Q000209:etiology / Q000276:immunology*; D016918:Arthritis, Reactive / Q000209:etiology / Q000276:immunology; D001426:Bacterial Proteins / Q000032:analysis / Q000276:immunology*; D003429:Cross Reactions; D006680:HLA Antigens / Q000276:immunology*; D015235:HLA-B Antigens; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012760:Shigella / Q000276:immunology* / Q000472:pathogenicity; D012763:Shigella flexneri / Q000276:immunology / Q000472:pathogenicity; D013167:Spondylitis, Ankylosing / Q000209:etiology / Q000276:immunology; D014774:Virulence
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D006680:HLA Antigens; D015235:HLA-B Antigens