HIGH PREVALENCE OF ANTIBODIES AGAINST BETA(1)-ADRENOCEPTORS AND BETA(2)-ADRENOCEPTORS IN PATIENTS WITH PRIMARY ELECTRICAL CARDIAC ABNORMALITIES

Objectives. This study sought to determine the prevalence of autoantib odies directed against the beta adrenoceptors in patients with primary electrical cardiac abnormalities, including atrial arrhythmias, ventr icular arrhythmias and conduction disturbances, in the absence of any other cardiac abnormality, Background. Using synthetic peptides corres ponding to the predicted sequences for the second extracellular loop o f the human beta(1)- and beta(2)-adrenoceptors as antigenic targets, a utoantibodies directed against the beta-adrenoceptors were recently sh own to occur in patients with idiopathic dilated cardiomyopathy and Ch agas' heart disease. Methods. Eighty-six patients (57 with primary ele ctrical abnormalities, 29 with idiopathic dilated cardiomyopathy) and 101 healthy and cardiopathic control subjects were studied, Antibodies against the beta(1)- and beta(2)-peptides were detected with an enzym e immunoassay performed in blinded manner. In nine selected (seroposit ive) cases, the immunoglobulin G (IgG) fraction was tested for functio nal effects on the rate of beating of cultured neonatal rat cardiomyoc ytes. Results, Antibodies recognizing the beta(1)- and beta(2) peptide s 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) a nd 11 (37.9%) of 29 patients with dilated cardiomyopathy (p < 0.05) co mpared with 15 (14.8%) of 101 control subjects, A rapid increase in th e rate of beating of the cultured cardiomyocytes was induced by IgG fr om a selected group of patients, suggesting an agonist like interactio n with a functional epitope, This response was mediated by stimulation of both the beta(1) and beta(2)-adrenoceptors in the patients with pr imary ventricular arrhythmias but only the beta(1)-adrenoceptors in th e patients with idiopathic dilated cardiomyopathy. Conclusions, Primar y ventricular arrhythmias and conduction disturbances, like idiopathic cardiomyopathy, show a high prevalence of antibodies interacting with functional epitopes of the beta-adrenoceptors, suggesting a common or similar abnormal immunoregulatory process.