Autoantibodies against beta-adrenoceptors in human idiopathic dilated cardiomyopathy.

Abstract

Although it is recognized that the number of cardiac beta-adrenoceptors is reduced in human dilated cardiomyopathy, the mechanisms involved have not been defined. We examined the possible role of altered humoral immunity by comparing the effect of sera from patients with idiopathic dilated cardiomyopathy (n = 20), ischemic or valvular heart disease (n = 28), or controls with no known cardiac disease (n = 18) on the binding of radioligands to cardiac beta-receptors. The ability of sera from cardiomyopathic patients to inhibit the binding of [3H]dihydroalprenolol to rat cardiac membranes was significantly higher than that of the other two patient groups (40 +/- 5% at 50-fold serum dilution compared to 14 +/- 3% for the ischemic/valvular heart disease group, and 14 +/- 4% for the normal control group, p less than 0.001). A similar inhibition was exerted by IgG from cardiomyopathic patients. Only the number, not the affinity, of the beta-receptors was decreased by cardiomyopathic sera. This decrease could be prevented by preincubating the sera with anti-human IgG, indicating the presence of autoantibodies. Furthermore, the sera were ineffective against cardiac alpha 1-adrenoceptors and considerably less effective against lung beta 2-receptors. In addition to ligand binding inhibition, sera from cardiomyopathic patients could immunoprecipitate beta-adrenoceptors quantitatively from solubilized cardiac membranes. Positive sera inhibited significantly isoproterenol-stimulated adenylate cyclase with no effect on basal or NaF-stimulated activities. These results document the presence in sera from patients with idiopathic dilated cardiomyopathy of autoantibodies directed against the cardiac beta 1-adrenoceptor which may play an important role in the regulation of inotropic responsiveness to beta-agonists.

Mimicry and Antibody-Mediated Cell Signaling in Autoimmune Myocarditis

“…In this study, Ab-mediated activation of PKA was identified in a rat heart cell line and was shown to be mediated by both ␤1-and ␤2-AR. These results are consistent with previous reports suggesting that sera from myocarditis and cardiomyopathy patients contain agonistic autoantibodies that bind to ␤-AR (34,37). Adrenergic receptors, especially ␤1 subtype, not only function to generate second messengers to control the heart contractility, but also to regulate other cardiac functions, myocyte growth, and programmed cell death.…”

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).…”

Profiling humoral autoimmune repertoire of dilated cardiomyopathy (DCM) patients and development of a disease‐associated protein chip

“…In particular, autoantibodies against cellular cardiac proteins, like G-protein coupled receptors (e.g., b 1 -adrenergic receptors [13,14]) and muscarinergic receptors (M2), have been identified [15]. In addition, antibodies against membrane components and mitochondrial proteins, especially against the ADP/ATP-carrier protein of the inner mitochondrial membrane, have been associated with the disease [16,17].…”