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(Circulation. 1999;99:649-654.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Autoantibodies Activating Human ß1-Adrenergic Receptors Are Associated With Reduced Cardiac Function in Chronic Heart Failure
From the Medizinische Poliklinik (R.J., G.I., F.B.) and the Institut für Pharmakologie (R.J., V.B., C.S., M.J.L.), University of Würzburg, Germany.
Correspondence to Dr Fritz Boege, Medizinische Poliklinik der Universität Würzburg, Klinikstraße 6-8, D-97070 Würzburg, Germany. E-mail boege.medpoli{at}mail.uni-wuerzburg.de
Background—Autoantibodies against synthetic peptides of ß-adrenergic receptors have been observed in human cardiomyopathy. However, it has never been shown that such antibodies really interact with native human ß-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 ß-receptor peptides. Such IgGs were further analyzed for binding and functional interactions with native recombinant human ß-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 ß-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 µmol/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 ß-adrenergic receptors exist in 
25% of patients with
dilated cardiomyopathy. Counteraction of such
autoantibodies might contribute to the beneficial effects of
ß-adrenergic receptor blockade in chronic heart failure.
Key Words: antibodies • receptors, adrenergic, beta • cardiomyopathy • immune system
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