Autoantigen estimation and simple screening assay against cardiodepressant Autoantibodies in patients with dilated cardiomyopathy

The objective of this study was to identify the cardiodepressant autoantibodies that could directly influence left ventricular ejection fraction (LVEF) in patients with dilated cardiomyopathy (DCM), as well as to establish a simple screening method for these antibodies. Not only acute hemodynamic but also chronic prognosis improvements were reported with immunoadsorption in some patients with DCM. Various antibodies determined by immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay (beta 1-adrenergic [beta 1-] receptors, muscarinic M2-acetylcholine [M2-] receptors, troponin I, or Na-K-ATPase) were measured in 104 patients with DCM. Cardiodepressant antibodies were also determined by ultrasonic echocardiography (UCG) of 18 day old chick embryos after adding the patients' purified immunoglobulin G, and the following clinical features were compared: age, gender, New York Heart Association class, LVEF, neurohumoral factors, arrhythmias, and other antibodies. We also checked the in vitro immunoadsorption effect against these cardiodepressant antibodies. Cardiodepressant antibodies were found in 63% of 104 patients with DCM and had no relation to other clinical parameters, except for some antibodies such as anti-beta 1-receptor antibodies (81% vs. 52%, P < 0.01), anti-M2-receptor antibodies (83% vs. 48%, P < 0.01), or anti-Na-K-ATPase antibodies (85% vs. 55%, P < 0.01). However, cardiodepressant antibodies were similarly found in patients with and without antibodies against troponin I (56% vs. 64%). The LVEF of chick embryos measured by UCG in the presence of patient serum was improved after in vitro immunoadsorption. The ex vivo system using chick embryos was able to determine cardiodepressant antibodies. By multivariate analysis, antibodies against beta 1- or M2-receptors was a predictor of these autoantibodies.