Systemic Lupus Erythematosus (SLE) and Polymyositis (PM) are two disorders associated with disease specific autoantibodies. In SLE, a family of immune responses against several RNAprotein particles is characteristic of the disease. One of these, the Ro/SSA particle is of particular interest because of anti-Ro/SSA is characteristic of several lupus disease subsets and there is strong evidence for a number of genes (e.g., Class II, T cell receptor) that strongly influence its production. Three components of this program project focus on three related aspects of the immunochemistry, genetics, and clinical aspects of the Ro/SSA-antiRo/SSA system. In one project, Dr. John Harley will characterize the sequential epitopes on the lymphocyte 60 kDA Ro/SSA protein. In a second, Dr. Bart Frank will characterize the T cell beta chain gene polymorphism that is associated with a major subset of patients producing response to the RBC 60 kDa Ro/SSA protein and its relationship to nephritis. The relationships among these three projects are manifold and complementary. Dr. Ira Targoff will continue his studies on several disease specific antibodies in polymyositis in which the targets are translation related proteins. Three previously undescribed translation related factors that are disease specific antigenic targets in this disease will be cloned and sequenced. Dr. Targoff will determine if in addition to recognized Class II polymorphism (DRw52) that associate with antibodies to translation related factors, there are also T cell receptor gene polymorphisms that are associated. These projects are all directed to analysis of disease specific autoantibodies at several levels: molecular characterization of the antigens, definition of genetic factors at the various loci that affect autoimmune responses, and relationship of these antibodies to disease expression in autoimmunity.
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