Genetic basis of myocarditis: A paradigm based on myosin heavy chain polymorphisms

The relationship between myocarditis and enteroviral infection is well established. However, the pathogenetic link between viral cytopathogenicity, myocardial autoantigens, and the immune system is only now beginning to unfold. Experimental evidence strongly points to a post-infectious autoimmune etiology of myocarditis. The first stage of myocarditis, usually associated with scanty myocyte damage, results from a direct viral infection. Accordingly, the immune response is directed against the virus and protects against myocardial damage. Some mouse strains, however, develop a second stage characterized by diffuse myocardial inflammation and anticardiac immune response. Recent progress in our understanding of myocarditis is reviewed with special attention to the autoimmune phase of the process. Data which suggest the importance of genes situated on chromosome 14 in mice, including the myhc-α gene, are discussed. In addition, the role of myhc-α polymorphisms in determining susceptibility to autoimmune myocarditis is considered.