Preeclampsia Linked to Angiotensin Autoantibodies

A recent publication presented evidence suggesting that preeclampsia (abnormal hypertension and proteinuria in pregnancy) is an autoimmune disease in which angiotensin receptor–activating autoantibodies contribute to many features of the disease.

Preeclampsia affects approximately five percent of pregnancies and remains a leading cause of maternal and neonatal mortality and morbidity. The clinical hallmarks of this 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 preeclampsia is unavailable owing to the poor understanding of the pathogenesis of the disease.

In the current study, investigators at the University of Texas Medical School (Houston, TX, USA) looked at the possible involvement of angiotensin, an oligopeptide in the blood that causes vasoconstriction and increased blood pressure. Numerous recent studies had shown that women with preeclampsia possessed autoantibodies termed AT1-AAs, which bound and activated the angiotensin II receptor type 1a (AT1 receptor).

To this end, the investigators injected pregnant mice with either total IgG or affinity-purified AT1-AAs isolated from women with preeclampsia. Results published in the July 27, 2008, online edition of the journal Nature Medicine, revealed that after being injected the mice developed key features of preeclampsia, including hypertension, proteinuria, glomerular endotheliosis (a classical renal lesion of preeclampsia), placental abnormalities, and small fetus size. Development of these features could be prevented by co-injection with the anti-hypertension drug losartan, an AT1 receptor antagonist. These results provided strong experimental support for the hypothesis that preeclampsia is an autoimmune disease in which angiotensin receptor–activating autoantibodies contribute to many features of the disease.

"There is no effective treatment for preeclampsia other than delivery, in part because of the lack of complete understanding of the disease,” said associate author Dr. Susan Ramin, professor of obstetrics, gynecology, and reproductive sciences at the University of Texas Medical School. "Using the animal model we were able to prevent preeclampsia in pregnant mice. I do not want to overstate the implications, but this is clearly a very exciting time for all of us involved in the research. We plan to focus our efforts in expanding this research to pregnant women.”


Related Links:
University of Texas Medical School