Cardiac Autoantibodies to Myosin and Other Heart-specific Autoantigens in Myocarditis and Dilated Cardiomyopathy

Abstract

Dilated cardiomyopathy (DCM) is characterized by dilation and impaired contraction of the left ventricle or both; it is a relevant cause of heart failure and a common indication for heart transplantation. It may be idiopathic, familial/genetic, viral, autoimmune or immune-mediated, associated with a viral infection. Myocarditis is an inflammatory disease of the myocardium; it may be idiopathic, infectious or autoimmune and may heal or lead to DCM. Thus, in a patient subset, myocarditis and DCM are thought to represent the acute and chronic stages of an organ-specific autoimmune disease of the myocardium. In keeping with this hypothesis, autoimmune features in patients with myocarditis/DCM include: familial aggregation, a weak association with HLA-DR4, abnormal expression of HLA class II on cardiac endothelium on endomyocardial biopsy, detection of organ-and disease-specific cardiac autoantibodies in the sera of affected patients and of symptom-free relatives. The organ-specific cardiac autoantibodies detected by immunofluorescence are directed against multiple antigens. One of these, first identified using immunoblotting and confirmed by ELISA, is the cardiac-specific α-myosin isoform. Myosin fulfils the expected criteria for organ-specific autoimmunity, in that immunization with cardiac but not skeletal myosin reproduces, in susceptible mouse strains, the human disease phenotype of myocarditis/DCM; in addition, a-myosin is entirely cardiac-specific. The organ-specific cardiac autoantibodies detected by immunofluorescence in symptom-free relatives were associated with echocardiographic features suggestive of early disease. Short-term follow-up is in keeping with this interpretation, although extended follow-up is necessary to define better the role of the antibody as predictor of disease susceptibility in healthy subjects at risk of myocarditis/DCM, such as first-degree relatives.

Key Words:

• Dilated cardiomyopathy
• Familial
• Myocarditis
• Autoimmunity
• Autoantibodies
• myosin