Autoantibodies produced against sarcolemmal Na-K-ATPase: possible upstream targets of arrhythmias and sudden death in patients with dilated cardiomyopathy.

Abstract

We sought to test the hypothesis that autoantibodies (Abs) produced against sarcolemmal Na-K-ATPase play a role in the development of ventricular tachycardia (VT) and cardiac sudden death in patients with dilated cardiomyopathy (DCM). Autoimmunity is one of the mechanisms of pathogenesis of DCM as well as virus infection and genetic predisposition. One hundred patients with DCM and age-matched control subjects (CTL) were screened for Abs produced against Na-K-ATPase by using enzyme-linked immunosorbent assay. Abs were detected in 26 DCM and 2 CTL patients. Na-K-ATPase activity in the presence of patient IgG was lower in DCM with Abs than without Abs, but there was no difference between two groups in CTL. Western blots showed that Abs recognized the alpha subunit of Na-K-ATPase, and 3H-ouabain bindings in the presence of patient IgG showed that dissociation constant was higher in DCM with Abs than without Abs. No difference existed between subjects with regard to age, gender, New York Heart Association functional class, cardiac function, or neurohormone levels, except for plasma norepinephrine, which was higher in patients with Abs than without Abs. VTs were more common in patients with Abs than without Abs, and multiple logistic regression analysis demonstrated that the presence of Abs, but not plasma norepinephrine, was an independent predictor for the occurrence of VT. Cardiac sudden death was independently predicted by the presence of Abs, as well as poor systolic function. We conclude that there are Abs produced against sarcolemmal Na-K-ATPase in patients with DCM and that Abs could be responsible for the electrical instability in some cases.