Beta 1-adrenergic receptor-directed autoimmunity as a cause of dilated cardiomyopathy in rats.
Progressive cardiac dilatation and pump failure of unknown etiology has been termed idiopathic dilated cardiomyopathy (DCM). During recent years a large body of data has accumulated indicating that functionally active antibodies or autoantibodies being able to recognize and to stimulate the cardiac beta(1)-adrenergic receptor (anti-beta(1)-AR) may play an important role in the initiation and/or clinical course of DCM. Recent experiments in rats even point towards a cause-and-effect relation between stimulatory anti-beta(1)-AR antibodies and DCM. Immunization of rats against the second extracellular loop of the human beta(1)-adrenergic receptor (100% sequence-identity between human and rat) resulted in both development of stimulatory anti-beta(1)-AR antibodies and development of progressive cardiac dilatation and dysfunction. Isogenic transfer of stimulatory anti-beta(1)-AR from cardiomyopathic into healthy inbred animals reproduced the disease, hence providing conclusive proof for a beta(1)-receptor-directed autoimmune attack as a possible cause of cardiomyopathy. This kind of cardiomyopathy is now referred to as anti-beta(1)-AR-induced dilated immune-cardiomyopathy (DiCM). The following article reviews recent evidence obtained from experimental animal-models implying a significant role of the cardiac beta(1)-adrenergic receptor as a pathophysiologically and clinically relevant autoantigen also in human DCM.
Jahns
Roland
R
Department of Internal Medicine, Medizinische Klinik und Poliklinik I, University of Wuerzburg, Josef-Schneider-Strasse 2, D-97080 Wuerzburg, Germany. jahns_r@klinik.uni-wuerzburg.de
Boivin
Valérie
V
Lohse
Martin J
MJ
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D015551:Autoimmunity / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D009200:Myocardial Contraction / Q000276:immunology; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000276:immunology*
D000319:Adrenergic beta-Antagonists; D001323:Autoantibodies; D001324:Autoantigens; D018342:Receptors, Adrenergic, beta-1