Autoantibodies against the beta- and muscarinic receptors in cardiomyopathy.
The sera of patients with idiopathic dilated cardiomyopathy and the Chagas' disease contain agonist-like autoantibodies directed against the beta 1-adrenoceptor and/or the muscarinic M2-receptor. The anti-beta 1-adrenoceptor antibodies could be directed against amino acid sequences of the first or second extracellular loop. In patients with dilated cardiomyopathy the first as well as the second extracellular loop was identified as an antibody epitope. In Chagas' disease the anti-beta 1-adrenoceptor antibody recognizes only 1 epitope on the second extracellular loop. The anti-beta 1-adrenoceptor antibodies acting like the beta-adrenergic agonist isoprenaline and exert a positive chronotropic effect in cultured rat cardiomyocytes. In contrast to isoprenaline the antibody caused no downregulation of the beta-adrenergic signal transduction cascade within 6 hours. The anti-M2 receptor antibodies recognize in both diseases an epitope on the second extracellular loop. The anti-M2-receptor antibody exert a negative chronotropic response in cultured cardiomyocytes. This antibody induced no downregulation of the muscarinic M2-receptor. The negative chronotropic effect was unabated for 6 hours. Based on these findings it is believed that the agonist-like autoantibodies that act against the beta 1-adrenoceptor and the muscarinic M2-receptor may play a role in the pathogenesis of dilated cardiomyopathy and Chagas' disease.
Wallukat
G
G
Max Delbrück Centrum für Molekulare Medizin, Berlin, Germany. gwalluk@mdc-berlin.de
Nissen
E
E
Morwinski
R
R
Müller
J
J
D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000276:immunology*; D009202:Cardiomyopathies / Q000175:diagnosis / Q000276:immunology*; D002598:Chagas Cardiomyopathy / Q000175:diagnosis / Q000276:immunology; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D043585:Receptor, Muscarinic M2; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*; D011976:Receptors, Muscarinic / Q000276:immunology*
D001323:Autoantibodies; D043585:Receptor, Muscarinic M2; D018342:Receptors, Adrenergic, beta-1; D011976:Receptors, Muscarinic