Autoantibody Profiling in Cardiomyopathies: Toward Immune-Guided Risk Stratification and Therapy.

Cardiomyopathies comprise a heterogeneous group of myocardial disorders characterized by structural and/or functional abnormalities in the absence of secondary causes of myocardial dysfunction. Although genetic determinants play a central role in many forms of the disease, incomplete penetrance and the frequent absence of identifiable pathogenic variants suggest that additional mechanisms contribute to disease onset and progression. Growing evidence supports the pathogenic role of autoimmune processes in several cardiomyopathy phenotypes. A spectrum of autoantibodies targeting cardiac self-antigens, including structural proteins, intercalated disc components, intracellular proteins such as calreticulin, and G protein-coupled receptors, has been identified in affected patients. Experimental and clinical data suggest that these autoantibodies may exert functional effects on cardiomyocyte signaling pathways and intercellular coupling, thereby promoting maladaptive remodeling, progressive ventricular dysfunction, and an increased risk of arrhythmias. Accordingly, autoantibody profiling may facilitate the identification of biologically distinct cardiomyopathy subsets with potential diagnostic and prognostic implications. From a therapeutic perspective, pathogenic autoantibodies can be removed from patient serum through plasmapheresis or immunoadsorption strategies, and these approaches have been associated with improvements in hemodynamic parameters and clinical outcomes in selected patients.