Differential profile and biochemical effects of antiautonomic membrane receptor antibodies in ventricular arrhythmias and sinus node dysfunction

Background-The relationship between anti-beta -adrenergic (anti-betaR) and anti-M-2-cholinergic (anti-M2R) receptor anti bodies (Abs) and cardiac arrhythmias and their biochemical effects have not been systematically investigated. Methods and Results-We studied 41 patients, 28 with ventricular arrhythmias (primary or due to Chagas' heart disease or idiopathic dilated cardiomyopathy; group I), 13 with sinus node dysfunction (primary or caused by Chagas' heart disease; group II), and 10 healthy controls (group III). The chronotropic effects of the IgG and immunopurified anti-beta (1)RAbs or anti-M2RAbs were assessed on cultured cardiomyocytes before and after exposure to atropine and propranolol. The biochemical effects of the IgG from 9 patients from group I, 6 from group II, and 6 controls were evaluated on COS7 cells transfected with genes encoding for PI,P? adrenergic receptors (cAMP increment) or M-2-cholinergic receptors (phosphatidylinositol increment). The IgG from group I patients exerted a positive chronotropic action, with a high prevalence of anti-beta RAbs (75%) and low prevalence of anti-M2RAbs (10.7%) and induced a clear-cut and long-lasting increment in cAMP. The IgG from group II patients depressed chronotropism, with a high prevalence of anti-M2RAbs (76.9%) and low prevalence of anti-beta RAbs (15.4%) and evoked a marked augmentation of phosphatidylinositol. Conclusions-Our results demonstrate a strong correlation between anti-beta RAbs and ventricular arrhythmias and anti-M2RAbs and sinus node dysfunction. Anti-beta RAbs increase and anti-M2RAbs inhibit cAMP production. These findings offer new insight into the etiology and pathophysiology of cardiac arrhythmias, with therapeutic implications.