Autoantibodies and cardiomyopathy: Focus on Beta1-adrenergic receptor autoantibodies.

ABSTRACT: Antibody response to self-antigens leads to autoimmune response that plays a determinant role in cardiovascular disease outcomes including dilated cardiomyopathy. Although the origins of the self-reactive endogenous autoantibodies is not well characterized, it is thought to be triggered by tissue injury or dysregulated humoral response. Autoantibodies that recognize G-protein coupled receptors (GPCRs) are considered consequential as they act as modulators of downstream receptor signaling displaying a wide range of unique pharmacological properties. These wide range of pharmacological properties exhibited by autoantibodies has cellular consequences that is associated with progression of disease including dilated cardiomyopathy. Increase in autoantibodies recognizing beta1-adrenergic receptor (β1AR), a GPCR critical for cardiac function is observed in patients with dilated cardiomyopathy. Cellular and animal model studies have indicated pathological roles for the β1AR autoantibodies, but less is understood about the molecular basis of their modulatory effects. Despite the recognition that β1AR autoantibodies could mediate deleterious outcomes, emerging evidence suggests that not all β1AR autoantibodies are deleterious. Recent clinical studies show that β1AR autoantibodies belonging to the IgG3 sub-class is associated with beneficial cardiac outcomes in patients. This suggests that our understanding on the roles the β1AR autoantibodies play in mediating outcomes is not well understood. Technological advances including structural determinants of antibody binding could provide insights on the modulatory capabilities of β1AR autoantibodies in turn, reflecting their diversity in mediating β1AR signaling response. Here we discuss the significance of the diversity in signaling and its implications in pathology.