Genetically determined myocarditis: clinical presentation and immunological characteristics

Myocarditis is a clinically heterogeneous myocardial inflammatory disease, diagnosed by endomyocardial biopsy; it may be idiopathic, infectious, or autoimmune and may lead to dilated cardiomyopathy. Myocarditis and dilated cardiomyopathy represent different stages of an organ-specific autoimmune disease in genetically predisposed individuals.

In animal models, cell-mediated or antibody-mediated autoimmune myocarditis/dilated cardiomyopathy can be induced by viral infection or immunization with heart-specific autoantigens, or can develop spontaneously in genetically predisposed strains. Susceptibility is based on multiple major histocompatibility complex and nonmajor histocompatibility complex genes. In patients the diagnosis of autoimmune myocarditis/dilated cardiomyopathy requires exclusion of viral genome on endomyocardial biopsy and detection of serum heart-reactive autoantibodies. They are directed against multiple antigens that are found in patients and relatives from about 60% of familial and nonfamilial pedigrees. They predict dilated cardiomyopathy development among relatives, years before disease. Some antibodies have functional effects on cardiac myocytes in vitro, in animals and possibly in a dilated cardiomyopathy subset, responsive to extracorporeal immunoadsorption.

In myocarditis/dilated cardiomyopathy, cardiac-specific and disease-specific antibodies of IgG class are potential biomarkers for identifying 'at risk' relatives as well as those patients in whom, in the absence of active infection of the myocardium, immunosuppression, and/or immunomodulation may be beneficial. Future studies should better define the genetic basis of human autoimmune myocarditis/dilated cardiomyopathy.