Abstract
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.
Users
Please
log in to take part in the discussion (add own reviews or comments).