Mimicry and antibody-mediated cell signaling in autoimmune myocarditis

Abstract

The mechanisms by which autoantibodies against cardiac myosin (CM) may lead to heart dysfunction is unknown. We show that autoantibodies to CM in anti-CM sera and mAbs derived from experimental autoimmune myocarditis targeted the heart cell surface and induced Ab-mediated cAMP-dependent protein kinase A activity. Ab-mediated cell signaling of protein kinase A was blocked by CM, anti-IgG, or by specific inhibitors of the beta-adrenergic receptor (beta-AR) pathway. mAbs confirmed mimicry between CM and the beta-AR. Passive transfer of purified Ab (IgG) from CM-immunized rats resulted in IgG deposition and apoptosis in the heart, leading to a cardiomyopathic heart disease phenotype in recipients. Our novel findings link anti-CM Ab with the beta-AR and subsequent Ab-mediated cell signaling in the heart.