Letter abstract
Nature Medicine 14, 855 - 862 (2008)
Published online: 27 July 2008 | doi:10.1038/nm.1856
Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice
Cissy C Zhou1, Yujin Zhang1, Roxanna A Irani1, Hong Zhang2, Tiejuan Mi1, Edwina J Popek3, M John Hicks3, Susan M Ramin4, Rodney E Kellems1 & Yang Xia1
Pre-eclampsia affects approximately 5% of pregnancies and remains a leading cause of maternal and neonatal mortality and morbidity in the United States and the world1, 2. The clinical hallmarks of this maternal disorder include hypertension, proteinuria, endothelial dysfunction and placental defects. Advanced-stage clinical symptoms include cerebral hemorrhage, renal failure and the HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome. An effective treatment of pre-eclampsia is unavailable owing to the poor understanding of the pathogenesis of the disease. Numerous recent studies3, 4, 5 have shown that women with pre-eclampsia possess autoantibodies, termed AT1-AAs, that bind and activate the angiotensin II receptor type 1a (AT1 receptor). We show here that key features of pre-eclampsia, including hypertension, proteinuria, glomerular endotheliosis (a classical renal lesion of pre-eclampsia), placental abnormalities and small fetus size appeared in pregnant mice after injection with either total IgG or affinity-purified AT1-AAs from women with pre-eclampsia. These features were prevented by co-injection with losartan, an AT1 receptor antagonist, or by an antibody neutralizing seven–amino-acid epitope peptide. Thus, our studies indicate that pre-eclampsia may be a pregnancy-induced autoimmune disease in which key features of the disease result from autoantibody-induced angiotensin receptor activation. This hypothesis has obvious implications regarding pre-eclampsia screening, diagnosis and therapy.
- Departments of Biochemistry and Molecular Biology, University of Texas—Houston Medical School, 6431 Fannin, Houston, Texas 77030, USA.
- Department of Pathology, Baylor College of Medicine, 1200 Moursund Street, Houston, Texas 77030, USA.
- Department of Pathology of Texas Children's Hospital, 6621 Fannin, Houston, Texas 77030, USA.
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Texas—Houston Medical School, 6431 Fannin, Houston, Texas 77030, USA.
Correspondence to: Yang Xia1 e-mail: yang.xia@uth.tmc.edu
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