Functional Autoantibodies in Myocardial Diseases

Myocardial autoimmune responses result in distinctive cardiac diseases and are associated with poor clinical outcomes. Autoantibodies (AAbs) play a crucial role in myocardial humoral autoimmunity by targeting endogenous tissue, or "self-antigens." Myocardial tissue injury or myocyte disarray caused by AAbs triggers a cascade of defensive immunological responses that may lead to worsening biventricular remodeling. However, over the past decade, the concept of AAbs in myocardial diseases has shifted from viewing AAbs as uniformly deleterious to a more nuanced explanation of AAbs influencing downstream intracellular pathways with multiple possible outcomes. This paradigm shift arose from technological advances such as large language models for accelerated epitope screening and high-throughput protein assays that uncover complex autoimmune cross-reactivity and downstream intracellular signaling pathways. In this contemporary review article, we critically appraise the latest translational data on the role of AAbs in myocardial disease and provide a framework to encourage scientific endeavors in the development of new therapeutics for cardiomyopathies.