Activating autoantibodies against human beta-adrenergic receptors were present in 26% of patients with dilated cardiomyopathy versus 1% in healthy subjects, and associated with poorer cardiac function.
Case-Control (n=212)
Are autoantibodies activating human beta-1-adrenergic receptors associated with reduced cardiac function in patients with chronic heart failure?
Activating autoantibodies against human beta-1-adrenergic receptors are present in a significant subset of patients with dilated cardiomyopathy and are associated with reduced left ventricular function, providing a potential mechanistic rationale for the efficacy of beta-blockers in heart failure.
Absolute Event Rate: 26% vs 1%
BACKGROUND: Autoantibodies against synthetic peptides of beta-adrenergic receptors have been observed in human cardiomyopathy. However, it has never been shown that such antibodies really interact with native human beta-adrenergic receptors, nor has the clinical impact of such an interaction been investigated in larger groups of patients. METHODS AND RESULTS: We screened 104 patients with dilated or ischemic cardiomyopathy (NYHA functional classes II to IV) and 108 healthy subjects for IgG antibodies reacting with beta-receptor peptides. Such IgGs were further analyzed for binding and functional interactions with native recombinant human beta-adrenergic receptors. Antibodies reacting with synthetic receptor peptides were present in 51% of the patients. However, only a subgroup directed against the second extracellular receptor domain also recognized native human beta-adrenergic receptors situated in a cell membrane. All antibodies of this subgroup impaired receptor ligand binding and enhanced receptor-mediated signaling, which could be blocked by 5 micromol/L bisoprolol in vitro. Their prevalence was 1% in healthy subjects and 10% in ischemic cardiomyopathy, whereas it amounted to 26% in dilated cardiomyopathy and was associated with a significantly poorer left ventricular function. CONCLUSIONS: 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.
Jahns et al. (Tue,) conducted a case-control in Dilated or ischemic cardiomyopathy (n=212). Autoantibodies against human beta-1-adrenergic receptors vs. Healthy subjects was evaluated on Prevalence of activating autoantibodies against native human beta-adrenergic receptors. Activating autoantibodies against human beta-adrenergic receptors were present in 26% of patients with dilated cardiomyopathy versus 1% in healthy subjects, and associated with poorer cardiac function.