Agonist-like beta-adrenoceptor antibodies in heart failure.
Anti-beta1-adrenoceptor antibodies may play a harmful role, and the elimination 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 experiments, the antibody prevented the down-regulation of the beta-adrenoceptor-mediated chronotropic response. This lack of desensitization, which resulted in permanent stimulation, could also influence the Ca2+ homeostasis of cardiomyocytes. However, in longer-term (72 hours)-treated cells, the antibodies were able to decrease subtype-specific expression of the beta1 adrenoceptor. In animal experiments, it was shown that long-term immunization with a peptide corresponding to the second extracellular loop of the beta1 adrenoceptor induced a failing heart similar to that in dilated cardiomyopathy. In humans, we observed a remarkable correlation between disappearance of the antibodies and improvement of heart function. Furthermore, in anti-beta1-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 indicates that autoimmune processes may be involved in some patients with dilated cardiomyopathy.
Wallukat
G
G
Max Delbrück Center of Molecular Medicine, Berlin, Germany.
Müller
J
J
Podlowski
S
S
Nissen
E
E
Morwinski
R
R
Hetzer
R
R
D000318:Adrenergic beta-Agonists / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D006333:Heart Failure / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D007163:Immunosorbent Techniques; D007165:Immunosuppression Therapy; D009200:Myocardial Contraction; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*
D000318:Adrenergic beta-Agonists; D001323:Autoantibodies; D018342:Receptors, Adrenergic, beta-1