Idiopathic inflammatory myopathy (polymyositis, dermatomyositis, and related disorders) is a family of inflammatory diseases in which disease-specific autoantibodies occur an for which there is considerable indirect evidence pointing to a viral etiology. We have over the past several years, seen and studied and collected serum, blood, and muscle specimens from well over 375 patients suspected of having myositis. We have collected epidemiologic information on many patients. We have cloned, sequences, and expressed histidyl-tRNA synthetase HRS, the principal target autoantigen in idiopathic polymyositis and dermatomyositis and are analyzing its structure and promoter. We have extended the analysis of HLA antigens in the sets of myositis patients defined by autoantibodies using the sequence specific oligonucleotide hybridization/PCR method. We have analyzed promoter activity of the HRS gene and are currently investigating translational control of its synthesis. We have successfully obtained high level expression of HRS, purified it, and are attempting to crystallize it (with and without substrate) so as to obtain x-ray crystallographics structure. We have successfully cloned a mutant HRS with the first two exons removed in order to probe antigenic structure and tRNA binding. We have made substantial progress in attempts to clone isoleucyl and leucyl tRNA syntheses. Using recombinant HRS, we have developed a technique to identify individual B cell producing anti-HRS autoantibodies from patients with myositis. We are in the midst of an analysis of the V region used by individual cells making these autoantibodies.
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