Associations of GPCR autoantibodies with clinical, histological, metabolic and hemodynamic features in non-ischemic heart failure patients

Abstract Background Roughly one third of cases chronic heart failure (HF) are caused by genetic predisposition, metabolic stress and cardiac inflammation. Animal studies suggest that heart-reactive autoantibodies, most notably those directed against G-protein-coupled receptors (GPCR), could also play a pathogenetic role in the disease. However, so far, causal link between humoral GPCR-autoimmunity human non-ischemic other than Chagas' cardiomyopathy remains unclear. Purpose Here, we investigated possible associations GPCR autoantibodies with inflammatory, hemodynamic, functional parameters patients HF unrelated to Methods We prospectively included 95 newly diagnosed unknown origin. Basic characterization comprised transthoracic echocardiography, magnetic resonance imaging, coronary angiography right catheterization endomyocardial biopsy. Mitochondrial oxidative phosphorylation capacity coupling was measured using high-resolution respirometry permeabilized myocardial fibers. A panel candidate GPCR-autoantibodies determined validated certified immune-assays peripheral venous blood HF-patients 60 matched healthy individuals. Results were normalized total IgG. Among 10 determined, only for α1-adrenergic receptor (α1AR), β1-adrenergic (β1AR), muscarinic M5 (M5AR), angiotensin II type 1 (AT1R) 2 (AT2R) exhibited HF-associated alterations: Autoantibodies β1AR, M5R AT2R increased. α1AR AT1R decreased (Figure). These alterations significant (p<0.01), but not, or weakly, correlated markers inflammation, damage, hemodynamics, histology left ventricular inflammation judged T2-mapping. HF-patients, increased associated improved mitochondrial (r=−0.27, p=0.021), insulin resistance (r=−0.24 p=0.027). Conclusion(s) Some previously postulated confirmed thoroughly characterized HF-patients. association these function not traceable, which argues specific pathogenic role. Our data compatible multifaceted interactions myocardium potentially glucose metabolism, possibly indicating disease-modifying compensatory Funding Acknowledgement Type funding sources: Public Institution(s). Main source(s): Research comission Heinrich-Heine University Duesseldorf