High prevalence of antibodies against beta1- and beta2-adrenoceptors in patients with primary electrical cardiac abnormalities

Objectives. This study sought to determine the prevalence of autoantibodies directed against the beta-adrenoceptors in patients with primary electrical cardiac abnormalities, including atrial arrhythmias, ventricular arrhythmias and conduction disturbances, in the absence of any other cardiac abnormality. Background. Using synthetic peptides corresponding to the predicted sequences for the second extracellular loop of the human beta1- and beta2-adrenoceptors as antigenic targets, autoantibodies directed against the beta-adrenoceptors were recently shown to occur in patients with idiopathic dilated cardiomyopathy and Chagasʹ heart disease. Methods. Eighty-six patients (57 with primary electrical abnormalities, 29 with idiopathic dilated cardiomyopathy) and 101 healthy and cardiopathic control subjects were studied. Antibodies against the beta1- and beta2-peptides were detected with an enzyme immunoassay performed in blinded manner. In nine selected (seropositive) cases, the immunoglobulin G (IgG) fraction was tested for functional effects on the rate of beating of cultured neonatal rat cardiomyocytes. Results. Antibodies recognizing the beta1- and beta2-peptides were found in 11 (52.3%) of 21 patients with ventricular arrhythmias (p < 0.01), 5 (35.7%) of 14 patients with conduction disturbances (p < 0.05), 3 (13.6%) of 22 patients with atrial arrhythmias (p > 0.05) and 11 (37.9%) of 29 patients with dilated cardiomyopathy (p < 0.05) compared with 15 (14.8%) of 101 control subjects. rapid increase in the rate of beating of the cultured cardiomyocytes was induced by IgG from selected group of patients, suggesting an agonist-like interaction with functional epitope. This response was mediated by stimulation of both the beta1- and beta2-adrenoceptors in the patients with primary ventricular arrhythmias but only the beta1-adrenoceptors in the patients with idiopathic dilated cardiomyopathy. Conclusions. Primary ventricular arrhythmias and conduction disturbances, like idiopathic cardiomyopathy, show high prevalence of antibodies interacting with functional epitopes of the beta-adrenoceptors, suggesting common or similar abnormal immunoregulatory process.