Autoantibodies and Cardiomyopathy: Focus on Beta-1 Adrenergic Receptor Autoantibodies

Antibody response to self-antigens leads to autoimmune response that plays a determinant role in cardiovascular disease outcomes including dilated cardiomyopathy (DCM). Although the origins of the self-reactive endogenous autoantibodies are not well-characterized, it is believed to be triggered by tissue injury or dysregulated humoral response. Autoantibodies that recognize G protein-coupled receptors are considered consequential because 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 DCM. Increase in autoantibodies recognizing beta-1 adrenergic receptor (beta 1AR), a G protein-coupled receptor critical for cardiac function, is observed in patients with DCM. Cellular and animal model studies have indicated pathological roles for the beta 1AR autoantibodies but less is understood about the molecular basis of their modulatory effects. Despite the recognition that beta 1AR autoantibodies could mediate deleterious outcomes, emerging evidence suggests that not all beta 1AR autoantibodies are deleterious. Recent clinical studies show that beta 1AR autoantibodies belonging to the IgG3 subclass is associated with beneficial cardiac outcomes in patients. This suggests that our understanding on the roles the beta 1AR 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 beta 1AR autoantibodies in turn, reflecting their diversity in mediating beta 1AR signaling response. In this study, we discuss the significance of the diversity in signaling and its implications in pathology.

Automated summary

The antibody response to self-antigens plays a crucial role in cardiovascular disease. Autoantibodies that modulate receptor signaling have diverse effects, but their exact role and mechanisms are still not well-understood.