Functional Autoantibodies in Myocardial Diseases

Central Illustration. Historical Perspective on the Assessment and Functionality of Autoantibodies in Myocardial Diseases Shifting the autoantibody paradigm from a traditional “all-is-harmful” approach toward a more nuanced avenue as they may affect cell-signaling pathways, simultaneously with the development of assays for antibody detection leveraging an increased diagnostic power. Ab = antibody; Ag = antigen; CV = cardiovascular; ELISA = enzyme-linked immunosorbent assay; IL = interleukin; LLMs = large language models; PhIP-Seq = Phage ImmunoPrecipitation Sequencing; SPMs = specialized pro-resolving mediators; Th2 = T helper 2 cells; TGF-β = tissue growth factor beta; TNF-α = tissue necrosis factor alpha; Treg = regulatory T cells.

Figure 1. Pathophysiologic Mechanisms of Different Autoantibodies with Linkage to Phenotypical Features and Outcome The mechanisms by which various autoantibodies contribute to disease pathology via cell surface receptors such as G-protein coupled receptors or M2 muscarinic receptors, highlighting associations with clinical phenotypes and prognostic outcomes. Key pathways and interactions are depicted, emphasizing the role of autoantibodies in modulating cellular and molecular responses. Biomarkers = N-terminal pro–B-type natriuretic peptide. See text for details. Ab = antibody; AF = atrial fibrillation; B1-R = beta-adrenergic 1-receptor; BCDT = B-cell depletion therapy; CMyH = cardiac myosin heavy chain; DSG-2 = desmoglein-2; EF = ejection fraction; GDMT = guideline-directed medical therapy; HF = heart failure; HSP = heat shock protein; IVIG = intravenous immunoglobulin; LV = left ventricle; LVWT = left ventricular wall thickness; M2R = muscarinic acetylcholine receptor; N-CAD = N-cadherin; PCT = progenitor cell therapy; SCD = sudden cardiac death; VES = ventricular extrasystole.

Figure 2. Specific Autoantibodies Related to Distinctive Cardiac Phenotypes The relationship between specific autoantibodies and various cardiac conditions, including dilated cardiomyopathy, peripartum cardiomyopathy, diabetic cardiomyopathy, cardiovascular disease (CVD), arrhythmogenic cardiomyopathy, and conduction disorders. Highlights known autoantibodies implicated in myocardial diseases and heart failure. Ab = antibody; CMyH = cardiac myosin heavy chain; DSC-2 = desmocollin-2; DSG-2 = desmoglein-2; HSP = heat shock protein.