MOLECULAR MIMICRY - ANY ROLE IN THE PATHOGENESIS OF SPONDYLOARTHROPATHIES

Ankylosing spondylitis and reactive arthritis are seronegative spondyl oarthropathies, which are strongly associated with HLA-B27. Despite in tensive investigation, the basis for this association is not clear. Ho wever, in recent years one favored hypothesis to explain this linkage has been that of molecular mimicry, i.e., sharing of linear or conform ational epitopes common to microbial antigens and host structures. Dur ing the past few years several examples of molecular mimicry between H LA-B27 and microbial antigens have been described. Heat shock proteins , among others, have been considered as target candidates for autoimmu ne phenomena, because of the high degree of homology between bacterial and mammalian species. Reactive arthritis triggered by Yersinia or Sa lmonella provides a unique model for studying the pathogenetic mechani sms underlying human inflammatory joint diseases in general, because t he arthritogenic microbes are known and well-characterized. We have de scribed two bacterial proteins that share amino acid homology with HLA -B27, namely YadA (Yersinia adhesin) and OmpH, outer surface proteins of Yersinia and Salmonella, respectively. Notably, the area of identit y of these amino acid sequences is located in the same place on the HL A-B27 molecule as a hexapeptide identical between Klebsiella nitrogena se and HLA-B27, and a pentapeptide shared by a Shigella flexneri prote in and HLA-B27. We have investigated immune responses to a panel of sy nthetic peptides based on the HLA-B27-homologous portions of pathogen- specific antigens in patients with reactive arthritis and ankylosing s pondylitis. One third of the patients have antibodies to the synthetic peptides. However, instead of recognizing the HLA-B27-homologous port ion, the antibodies are directed against the flanking sequences of the synthetic peptides. The concept of the role of molecular mimicry betw een HLA-B27 and microbial antigens in the pathogenesis of spondyloarth ropathies is discussed, with a conclusion that no convincing evidence for its significance exists at the present.