Polymyositis (PM), an autoimmune inflammatory myopathy, is frequently associated with autoantibodies. One subgroup of PM patients, marked by certain disease--specific anti-cytoplasmic autoantibodies (ACA), has a high frequency of interstitial lung disease, arthritis, and possibly other features. These ACA include anti-Jo-1, directed at histidyl-tRNA synthetase, antibodies to other amino-acyl-tRNA synthetases, and antibodies to other factors involved in translation and protein synthesis. The reason for the association of this clinical subgroup with antibodies to translation-related proteins than antibodies to nuclear proteins because they are mRNA viruses that interact with the translational apparatus. In this project we will investigate aspects of these antibodies. First, we will analyze certain key antigens in the group. Antibodies labeled KJ, CJ, and JP react with translation-related antigens, but do not precipitate tRNA as the anti-synthetases do. We will study the biochemical and molecular structure and cellular role of the antigens, and clone sequence the genes for the antigens. This could establish their relationship to translation and determine whether interaction, homology, or complementarity with known viral structures may occur. Second, we will study the question of the possible original immunogenic form of the antigen by analyzing the newly identified antibody reacting with the multi-enzyme synthetase complex. Anti-OJ reacts with multiple synthetase complex components, and immunoprecipitates many synthetases, but fewer than expected forms of tRNA. The antigenic components and the significance of the limited tRNA will be determined. Third, we will determine whether genetic features of the T- cell receptor can be identified that are associated with the production of this group of antibodies, or with the commonest of these antibodies, anti- Jo-1. These studies may provide insight into the reasons these antigens became immunogenic, and the reasons this group of antibodies is associated with this syndrome.
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