title: Receptor-activating autoantibodies and disease: preeclampsia and beyond.
abstract: The research reviewed in this article provides examples of autoantibody-mediated receptor activation that likely contributes to disease. The classic example is Graves' hyperthyroidism, in which autoantibodies activate the thyroid-stimulating hormone receptor resulting in overproduction of thyroid hormones. Other compelling examples come from the cardiovascular literature and include agonistic autoantibodies targeting the cardiac β(1)-adrenergic receptor, which are associated with dilated cardiomyopathy. Autoantibodies capable of activating α(1)-adrenergic receptors are associated with refractory hypertension and cardiomyopathy. A prominent example is preeclampsia, a hypertensive disease of pregnancy, characterized by the presence of autoantibodies that activate the major angiotensin receptor, AT(1). AT(1) receptor-activating autoantibodies are also observed in kidney transplant recipients suffering from severe vascular rejection and malignant hypertension. AT(1) receptor-activating autoantibodies and antibodies that activate the endothelin-1 receptor, ET(A), are prevalent in individuals diagnosed with systemic sclerosis. Thus, the presence of agonistic autoantibodies directed to G protein-coupled receptors has been observed in numerous cardiovascular disease states. Rapidly emerging evidence indicates that receptor-activating autoantibodies contribute to disease, and that efforts to detect and remove these pathogenic autoantibodies or block their actions will provide promising therapeutic possibilities.
authors: Department of Biochemistry and Molecular Biology, The University of Texas Medical School, Houston, TX 77030, USA. yang.xia@uth.tmc.edu
authors: Yang
authors: Y
authors: Xia
authors: Rodney E
authors: RE
authors: Kellems
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D044022:Receptor, Endothelin A / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000276:immunology / Q000473:pathology / Q000628:therapy
chemical_list: D001323:Autoantibodies; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A