Heart-reactive antibody levels differentially associate with ventricular function in hereditary cardiomyopathies

gCMP are a major cause of cardiovascular morbidity and mortality. While agonistic anti-β1-adrenergic receptor antibodies (anti-β1AR-EC_II) have a recognized pathogenic role in idiopathic dilated cardiomyopathy (DCM), the relevance of HRA in gCMP remains unclear.

One hundred gCMP patients with confirmed genetic variants in cardiomyopathy genes were compared with 100 age- and sex-matched healthy individuals. Antibody reactivities were quantified using bead-based flow cytometric assays against cardiac antigens: The second extracellular loop of the β1 adrenergic receptor (β1AR-EC_II), Troponin I3 (TPI3), Tropomyosin 1 (TPM1), Myosin heavy chain 6 and 7 (MYH6, MYH7) and Myosin light chain 7 (MYL7).

gCMP patients showed higher anti-TPI3 and lower anti-TPM1 antibody levels compared to controls indicating increased induction of the former and loss of the latter in gCMP patients. Age and sex influenced HRA patterns in both groups. Anti-MYH6 and anti-TPM1 antibody levels were negatively associated with left ventricular ejection fraction (LVEF), both overall and within specific gCMP subtypes, including hypertrophic and arrhythmogenic cardiomyopathy. Additionally, anti-MYH6 antibody levels were negatively associated with right ventricular function, measured by tricuspid annular plane systolic excursion (TAPSE).

Our findings stress the diagnostic potential of HRA profiling and indicate that gCMP patients might profit from therapeutic targeting of HRA.