Functional autoantibody diseases: Basics and treatment related to cardiomyopathies

• Published in: Frontiers in bioscience Vol. 24; no. 1; pp. 48 - 95
• Main Authors: Becker, Niels-Peter, Goettel, Peter, Mueller, Johannes, Wallukat, Gerd, Schimke, Ingolf
• Format: Journal Article
• Language: English
• Published: Singapore 01.01.2019
• Subjects: Animals; Autoantibodies - immunology; Autoimmune Diseases - immunology; Autoimmune Diseases - therapy; Cardiomyopathies - immunology; Cardiomyopathies - therapy; Humans; Receptor, Muscarinic M2 - immunology; Receptors, Adrenergic, beta-1 - immunology; Receptors, G-Protein-Coupled - immunology; Signal Transduction - immunology
• ISSN: 1093-9946; 2768-6698; 1093-4715
• DOI: 10.2741/4709

In the 1970s, autoantibodies directed against G-protein-coupled receptors (GPCR, GPCR-AAB) were discovered. After receptor binding, GPCR-AAB trigger uncontrolled receptor mediated signal cascades, thus producing pathologies. Diseases associated with such functionally active autoantibody type (functional autoantibodies) can be called "functional autoantibody diseases". Here we focus exclusively on GPCR-AAB directed against the GPCR's extracellular loops. The GPCR's role in the pathogenesis and progression is accepted in idiopathic dilated cardiomyopathy and is increasingly considered in diseases such as Chagas' cardiomyopathy, peripartum cardiomyopathy, hypertension, diabetes mellitus and scleroderma and even dementia, complex regional pain syndrome and postural orthostatic tachycardia syndrome. We briefly summarize the mechanistic background of GPCR-AAB induced pathologies, mainly focused on autoantibodies targeting the β1-adrenergic and muscarinic 2 receptors, due to their importance for cardiomyopathies. Furthermore, treatment strategies for "functional autoantibody diseases", such as for GPCR-AAB removal (therapeutic plasma exchange, immunoadsorption) and GPCR-AAB attack (intravenous IgG treatment, B-cell depletion, GPCR-AAB binding and neutralization) are critically reflected with respect to their patient benefits focused on but not exclusive to patients with dilated cardiomyopathy.