Immunogenetics of the spondyloarthropathies in humans and in animal models

Journal/Book: Z Rheumatol 1998; 57 Suppl. 1: 3 (H 11). 1998;

Abstract: INSERM U477 & Institut de Rhumatologie Hôpital Cochin Paris Dissecting out the contribution of both genetic and environmental factors to the predisposition to spondyloarthropathies (SpA) has become a leading goal of research in this field. The part of genetics in predisposition to ankylosing spondylitis has been approximated to 50 - 90 % based on the risk of recurrence of disease in pairs of monozygotic twins. Although a major contributing role seems to be attributable to the HLA region it has now been firmly established that other genetic factors are involved. Familial studies are currently under progress to investigate the nature of these genes. Animal models have been useful to examine implication of both HLA-B27 and the immune system in the pathophysiology of SpA. Rats transgenic for HLA-B27 and human (2-microglobulin develop a spontaneous multisystem inflammatory disease analogous to human SpA here called rat-SpA. The primary role played by the immune system in this model has been demonstrated. It was shown that the gut joint and skin manifestations were dependent upon HLA-B27-expressing bone marrow derived cells and that T cells were necessary for the disease to arise. Surprisingly a prominent role was found for pathogenic CD4+ T cells. The specificity of peptides bound to B27 has been found to influence the incidence of arthritis in the rats. Proinflammatory mediators produced in the gut mucosa and in the joint have been studied. Several cytokines (IFN-( IL-1( and TNF-() are abundant in the colonic mucosa of affected rats as well as myeloperoxidase and inducible NO synthase activities. The profile is different in the synovial tissue where IL-6 and TGF-( are rather elevated. ... le

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