Autoimmune Mechanisms Underlying Dilated Cardiomyopathy

Autoimmune abnormalities, as well as viral infection and genetic abnormalities, appear to be major predisposing factors for dilated cardiomyopathy (DCM). Abnormalities of cell-mediated immunity are mainly involved in the onset of cardiomyopathy secondary to myocarditis. However, various antimyocardial antibodies are detected in the serum of patients with DCM. The appearance of these antibodies was considered to be an epiphenomenon associated with myocyte injury resulting from myocarditis, but recent findings have suggested that at least some of them are directly related to the pathophysiology of DCM. In particular, an autoantibody targeting the beta 1-adrenergic receptor that exhibits an agonist-like effect is related to the persistent myocardial damage resulting in DCM and provides substrates for fatal ventricular arrhythmias. In addition, an antibody for the muscarinic M2 receptor is related to atrial fibrillation, an antibody targeting Na-K-ATPase is closely related to sudden cardiac death as a result of fatal ventricular arrhythmias, and an autoantibody for troponin I increases the L-type calcium current and is related to the myocardial damage. Based on these findings, immunoadsorption therapy was developed to remove such autoantibodies in patients with refractory heart failure as a result of DCM. (Circ J 2009; 73: 602-607)