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.