Agonist-like beta-adrenoceptor antibodies in heart failure

Anti-beta(1)-adrenoceptor antibodies may play a harmful role, and the elimi nation of these antibodies could have beneficial effects for some patients with dilated cardiomyopathy. In vitro experiments showed that the antibody was able to influence the function of cultured cardiomyocytes. In these exp eriments, the antibody prevented the down-regulation of the beta-adrenocept or-mediated chronotropic response. This lack of desensitization, which resu lted in permanent stimulation, could also influence the Ca2+ homeostasis of cardiomyocytes. However, in longer-term (72 hours)-treated cells, the anti bodies were able to decrease subtype-specific expression of the beta(1) adr enoceptor. In animal experiments, it was shown that long-term immunization with a peptide corresponding to the second extracellular loop of the beta(1 ) adrenoceptor induced a failing heart similar to that in dilated cardiomyo pathy. In humans, we observed a remarkable correlation between disappearanc e of the antibodies and improvement of heart function. Furthermore, in anti -beta(1)-adrenoceptor-positive patients with dilated cardiomyopathy treated with the immunoadsorption technique, removal of the antibodies also led to improvement of cardiac function and quality of life. This finding indicate s that autoimmune processes may be involved in some patients with dilated c ardiomyopathy. (C)1999 by Excerpta Medica, Inc.