Autoimmunity in idiopathic dilated cardiomyopathy. Characterization of antibodies against the beta 1-adrenoceptor with positive chronotropic effect.

Abstract

The second extracellular loop of the beta 1-adrenoceptor is a specific target for antibodies with stimulatory activity detected in patients with idiopathic DCM. The antibodies have a positive chronotropic effect on isolated rat heart myocytes. Autoantibody stimulation does not cause the normal agonist-induced desensitization phenomena of the effector system. These findings could contribute to our understanding of the pathophysiological mechanisms of the autoantibodies and of the beneficial effect of beta 1-blocking agents in the treatment of patients with idiopathic DCM.

Prediction of Short-Term Outcomes in Patients With Idiopathic Dilated Cardiomyopathy Referred for Transplantation Using Standard Echocardiography and Strain Imaging

“…Its principle is the neutralization of circulating autoantibodies found in some patients with DCM. The usual target of immunoadsorption is anti-beta1-adrenergic receptor antibodies, as they are thought to modify beta-adrenergic receptor activity and to produce chronic increases in signal transduction that are harmful to the failing heart (15). Although some studies have documented the benefit of immunoadsorption, it remains unclear whether it produces longterm benefit.…”

Association of Heart Failure in Homozygous β-Thalassemia With the Major Histocompatibility Complex

“…Increased HLA antigen expression has been found in cardiac myocytes of patients with idiopathic dilated cardiomyopathy. 33,34 Circulating autoantibodies [35][36][37] and altered T-cell function 38 -41 induced by the major histocompatibility complex may lead to immune-mediated heart disease. Similarities between microbial antigens and self HLA molecules may result in autoimmune reaction after infections.…”

Contribution of Acquired Factors to the Pathogenesis of Dilated Cardiomyopathy - The Cause of Dilated Cardiomyopathy: Genetic or Acquired? (Acquired-Side) -

“…This autoantibody increased the beating rate of neonatal rat cardiomyocytes, but unlike the response to isoproterenol, this positive chronotropic effect showed little evidence of desensitization. 32 On the other hand, prolonged exposure to this autoantibody for 72 h was able to decrease the β1-adrenergic receptor protein and mRNA content. 33 Cardiac dysfunction mimicking cardiomyopathy can be recapitulated by repeated immunization with peptides corresponding to the second extracellular loop of this receptor.…”