Key result
Specific heart-reactive antibodies are altered in genetic cardiomyopathy and correlate inversely with LVEF.
Why the study?
While agonistic anti-β1-adrenergic receptor antibodies have a recognized pathogenic role in idiopathic dilated cardiomyopathy, the relevance of heart-reactive antibodies in hereditary cardiomyopathies remained unclear.
Do heart-reactive antibody levels differ between patients with genetic cardiomyopathies and healthy controls, and do they associate with ventricular function?
Case-Control (n=200)
Single-blind
No
Do heart-reactive antibody levels differ between patients with genetic cardiomyopathies and healthy controls, and do they associate with ventricular function?
Absolute Event Rate: 97% vs 78%
p-value: p=≤0.001
Patients with hereditary cardiomyopathies exhibit distinct heart-reactive antibody profiles compared to healthy controls, with higher anti-MYH6 and anti-TPM1 levels correlating with worse ventricular function.
Antibody profiling may stratify genetic cardiomyopathy severity; hypothesis-generating for prognostic biomarkers in prospective cohorts.
Background 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. Methods 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). Results 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). Conclusion Our findings stress the diagnostic potential of HRA profiling and indicate that gCMP patients might profit from therapeutic targeting of HRA.
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Schiffer et al. (2026) conducted a case-control in Genetic cardiomyopathies (HCM, DCM, ARVC, RCM) (n=200). Genetic cardiomyopathy (gCMP) and heart-reactive antibodies (HRA) vs. Age- and sex-matched healthy controls was evaluated on Anti-TPI3 and anti-TPM1 antibody binding levels and association of anti-MYH6/anti-TPM1 with LVEF (p=≤0.001).
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