Recent reports have described a syndrome of a rapidly progressive cardiomyopathy associated with AIDS. A high prevalence of myocarditis has also been described. The etiology of AIDS- associated cardiomyopathy is yet unknown although immunologic mechanisms may play a significant role in its pathogenesis. Our preliminary studies with eleven randomly selected AIDS patients reveal a 46% prevalence of circulating heart autoantibodies. Two of the patients with AIDS-associated cardiomyopathy had circulating heart autoantibodies, deposits of IgG within the myocardium and increased myocardial expression of histocompatibility antigens. The AIDS Clinical Research Center will serve as the source of patients. Three funded projects permit the systematic evaluation at six month intervals of 300 AIDS patients/year. These patients will serve as the cohort for longitudinal studies to define the incidence and prevalence of AIDS-associated cardiomyopathy. These results will be correlated with possible etiologic factors such as AIDS-risk group, prescribed drugs, opportunistic infections and serologic evidence of autoimmunity. All patients will receive periodic echocardiograms over the course of a year. Patients with echocardiographic criteria for cardiomyopathy will undergo endomyocardial biopsy. Immunohistochemical techniques and in situ hybridization of biopsy and autopsy material will be used to determine if AIDS- associated cardiomyopathy is associated with HIV infection of the heart or possibly some other viral or opportunistic non-viral infection. Indirect immunofluorescence and Western immunoblotting using patient serum will determine the prevalence of heart autoimmunity and characterizing the cardiac antigens to which these autoantibodies react. A cooperative effect of both humoral and cell-mediated immune cardiac injury will be sought by performing heart explant and endothelial cytotoxicity studies. This proposal represents an extension of our long research committment in human and experimental myocarditis. It takes advantage of new technology and established collaborations in cardiology, immunology, pathology and virology to study the immunopathogenesis of AIDS-associated cardiomyopathy.
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