Clinical Significance of Circulating Cardiac Autoantibodies in Dilated Cardiomyopathy and Myocarditis

Abstract

Dilated cardiomyopathy (DCM) may be idiopathic, familial/genetic, viral, autoimmune or immune-mediated associated with a viral infection. Myocarditis includes idiopathic, infectious or autoimmune forms of inflammation and may heal or lead to DeM. Thus, within a patient group, myocarditis and DCM represent the acute and chronic stages of an organspecific autoimmune disease. Autoimmune features in myocarditis/OCM include: familial aggregation, a weak association with HLA-DR4, an abnormal expression of HLA class II on endomyocardial biopsy, and presence of organ- and disease specific cardiac autoantibodies of IgG class in the sera of patients and symptom-free relatives. The cardiac autoantibodies detected by immunofluorescence are directed against multiple antigens. Two of these are the atrial-specific a- and the ventricular and skeletal muscle β-heavy chain isoform. The a-myosin isoform 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. Additional antigenic targets of heartreactive autoantibodies include sarcolemmal proteins, mitochondrial enzymes, β-adrenergic and muscarinic receptors; for some of these antibodies there is in vitro evidence for a functional role. The organ-specific cardiac autoantibodies detected by immunofluorescence in symptom-free relatives were associated with echocardiographic features suggestive of early disease. Mid-tenn follow-up suggests that these antibodies may provide markers of progression to DCM among symptom-free relatives with or without abnonnal echocardiographic findings.