Autoantibodies Activating Human β ₁ -Adrenergic Receptors Are Associated With Reduced Cardiac Function in Chronic Heart Failure

Abstract

Our data show that activating autoantibodies against human beta-adrenergic receptors exist in approximately 25% of patients with dilated cardiomyopathy. Counteraction of such autoantibodies might contribute to the beneficial effects of beta-adrenergic receptor blockade in chronic heart failure.

Adoptive passive transfer of rabbit β1-adrenoceptor peptide immune cardiomyopathy into the Rag2−/− mouse: Participation of the ER stress

“…This hypothesis is further supported by 3 major findings: 1) the antoantibodies exert agonistic and apoptotic effects in cultured cardiomyocytes (1,(4)(5)(6), 2) immunization with a synthetic peptide corresponding to a sequence in the second extracellular loop of the human adrenergic receptor (β 1 -EC II ) produces cardiomyopathy in a number of experimental animals (7)(8)(9)(10), and 3) removal of anti-β 1 -EC II antibodies improves cardiac function in the rabbit β 1 -EC II cardiomyopathy (11), and human dilated cardiomyopathy (12). Furthermore, isogenic transfer of sera from rats immunized with the β 1 -EC II peptide to healthy littermates produces cardiac morphology similar to the cardiomyopathic changes in the donor rats (9).…”

“…Auto-antibodies against the β 1 -adrenergic receptors, present in 30−40% of patients with idiopathic dilated cardiomyopathy (1,2), have been postulated to play an important role in the pathogenesis of human cardiomyopathy (3). This hypothesis is further supported by 3 major findings: 1) the antoantibodies exert agonistic and apoptotic effects in cultured cardiomyocytes (1,(4)(5)(6), 2) immunization with a synthetic peptide corresponding to a sequence in the second extracellular loop of the human adrenergic receptor (β 1 -EC II ) produces cardiomyopathy in a number of experimental animals (7)(8)(9)(10), and 3) removal of anti-β 1 -EC II antibodies improves cardiac function in the rabbit β 1 -EC II cardiomyopathy (11), and human dilated cardiomyopathy (12).…”

Prevalencia de autoanticuerpos contra receptores autonómicos en pacientes panameños con cardiopatía chagásica crónica y con otras formas de cardiopatía

“…Estos autooanticuerpos también se han observado con diferentes frecuencias en pacientes con cardiopatías de origen no chagásico, incluyendo cardiomiopatía idiopática dilatada, cardiomiopatías isquémicas, arritmias y trastornos de la conducción (7,14,15).…”

Contribution of Acquired Factors to the Pathogenesis of Dilated Cardiomyopathy - The Cause of Dilated Cardiomyopathy: Genetic or Acquired? (Acquired-Side) -

“…Both the LVEF and the cardiac output were lower in the autoantibody-positive group than in the autoantibodynegative group. 37 Cox proportional hazards analysis showed that positivity for this autoantibody was useful in predicting the overall death rate and cardiovascular death rate in DCM patients, in addition to pulmonary wedge pressure and the cardiac index, which are well-known conventional predictors (Acquired) Acquired Factors in DCM of death. This autoantibody was detected in 13% of patients with heart failure of ischemic etiology, but was not useful as a predictor of death.…”