Antibodies to extracellular regions of G protein-coupled receptors and receptor tyrosine kinases as one of the causes of autoimmune diseases

Abstract

One of the causes of autoimmune diseases is the production of antibodies to extracellular loops of hormonal receptors coupled with heterotrimeric G-proteins (GPCR) and to ectodomains of receptors with tyrosine kinase activity. In recent years, the range of these diseases has considerably extended, raising interest to the mechanisms of their genesis and actualizing the search for effective ways of their prevention and treatment. The antibodies against extracellular regions of α₁-, β₁- and β₂-adrenergic receptors and m2-muscarinic acetylcholine receptors (m2-MAChR) were found in patients with various forms of cardiomyopathy and other pathologies of the cardiovascular system; the antibodies against m3-MAChR were detected in Sjögren’s syndrome and biliary cirrhosis; the antibodies against angiotensin receptors type 2 were found in pregnant women with pre-eclampsia and in different forms of hypertension; the antibodies to thyroid-stimulating hormone receptor were detected in Graves’ disease and other autoimmune thyroid pathologies. The role of antibodies specific to the ectodomain of muscle specific receptor tyrosine kinase in the development of generalized myasthenia and those against the extracellular domain of platelet-derived growth factor receptor in the development of systemic sclerosis and other fibroses was shown. In the present review, we systematize and analyze the data on the molecular mechanisms that underlie the production of antibodies to GPCR and receptor tyrosine kinases and determine the development of autoimmune diseases they induce. Possible approaches toward their prevention and correction are also discussed.