Autoantibodies against sarcolemmal Na-K-ATPase in patients with dilated cardiomyopathy: autoimmune basis for ventricular arrhythmias in patients with congestive heart failure

BACKGROUND: Autoimmunity is one of the mechanisms of pathogenesis of idiopathic dilated cardiomyopathy (DCM) as well as virus infection and genetic predisposition. Autoantibodies against sarcolemmal Na-K-ATPase may be involved in the development of ventricular tachycardia and cardiac sudden death in patients with DCM. METHODS AND RESULTS: By using enzyme-linked immunosorbent assay, autoantibodies were detected in 26% patients with DCM and in 2% age-matched control subjects. Na-K-ATPase activity in the presence of patient IgG was lower in patients with autoantibodies than without autoantibodies, but there was no difference in the control subjects. Western blots showed that autoantibodies recognized the alpha-subunit of Na-K-ATPase, and 3H-ouabain bindings in the presence of patient IgG showed that the dissociation constant was higher in patients with autoantibodies than without autoantibodies, although maximal binding sites were similar between the two groups. No difference existed between subjects with regard to age, sex, New York Heart Association functional class, cardiac function, or neurohormone levels, except for plasma norepinephrine which was higher in patients with autoantibodies than without autoantibodies, Ventricular arrhythmias were more common in patients with autoantibodies than without autoantibodies, and multiple logistic regression analysis demonstrated that the presence of autoantibodies, but not plasma norepinephrine, was an independent predictor for the occurrence of ventricular tachycardia. Cardiac sudden death was independently predicted by the presence of autoantibodies, as well as poor systolic function. CONCLUSIONS: Patients with DCM express autoantibodies against sarcolemmal Na-K-ATPase, and these autoantibodies could be responsible for the electrical instability in some patients.