Symposium Immunol Res 1993;12:193-208 Riitta Lahesmaa Mikael Skurnik Paavo Toivanen Department of Medical Microbiology, Turku University, Turku, Finland Molecular Mimicry: Any Role in the Pathogenesis of Spondyloarthropathies? Key Words Ankylosing spondylitis Reactive arthritis Yersinia Klebsiella HLA-B27 I . o * * o . o . o . * * * * o ~ 1 7 6 1 7 6 1 7 6 ot o . o o t t ~ 1 7 6 1 7 6 1 7 6 o o * * l * o Abstract Ankylosing spondylitis and reactive arthritis are seronegative spondyloar- thropathies, which are strongly associated with HLA-B27. Despite inten- sive investigation, the basis for this association is not clear. However, in recent years one favored hypothesis to explain this linkage has been that of molecular mimicry, i.e., sharing of linear or conformational epitopes com- mon to microbial antigens and host structures. During the past few years several examples of molecular mimicry between HLA-B27 and microbial antigens have been described. Heat shock proteins, among others, have been considered as target candidates for autoimmune phenomena, be- cause of the high degree of homology between bacterial and mammalian species. Reactive arthritis triggered by Yersinia or Salmonella provides a unique model for studying the pathogenetic mechanisms underlying human inflammatory joint diseases in general, because the arthritogenic microbes are known and well-characterized. We have described two bacte- rial 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 identity of these amino acid sequences is located in the same place on the HLA-B27 molecule as a hexapeptide identical between Klebsiella nitrogenase and HLA-B27, and a pentapeptide shared by a Shigellaflexneri protein and HLA-B27. We have investigated immune responses to a panel of synthetic peptides based on the HLA-B27-homologous portions of pathogen-specific antigens in pa- tients with reactive arthritis and ankylosing spondylitis. One third of the patients have antibodies to the synthetic peptides. However, instead of recognizing the HLA-B27-homologous portion, the antibodies are di- rected against the flanking sequences of the synthetic peptides. The con- cept of the role of molecular mimicry between HLA-B27 and microbial antigens in the pathogenesis of spondyloarthropathies is discussed, with a conclusion that no convincing evidence for its significance exists at the present. Dr. Paavo Toivanen Department of Medical Microbiology Turku University FIN-20520 Turku (Finland) 9 S. KargerAG, Basel 0257-277X/93/ 0122-019352.75/0