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CCMTR Research Finds Gene Regulating Immune System is Linked to Preeclampsia

Researchers at North Carolina State University’s Center for Comparative Medicine and Translational Research have discovered that the placentas of women who suffer preeclampsia during pregnancy have an overabundance of a gene associated with the regulation of the body’s immune system. Their discovery may lead to improved screening and prenatal care for these patients and their babies.

The results of the study are published in the February issue of the journal Placenta.

Preeclampsia occurs in up to 10 percent of all pregnancies, and is responsible for about 15 percent of pre-term births. The disorder is usually marked by a rapid rise in blood pressure that can lead to stroke, seizures or organ failures in the mother. Researchers have recently begun looking at preeclampsia as an autoimmune disorder, in which the mother’s body treats the placenta like an invader, but they weren’t sure of the genetic mechanisms involved.

Dr. Jorge Piedrahita, professor of genomics in the Department of Molecular Biomedical Sciences, along with other colleagues from the Center for Comparative Medicine and Translational Research and the Duke University School of Medicine, examined the genetic makeup of placentas from women with preeclampsia and compared the results to those from normal pregnancies.

“When we looked at the preeclampsic placentas, we found that several genes associated with a particular autoimmune pathway were ‘upregulated’ – basically, that there were more of them in placentas of preeclampsic women than in normal placentas,” Dr. Piedrahita says. “More specifically, we found the upregulation of a particular enzyme involved in sialic acid modification called SIAE. Sialic acid coats every cell in our body, making it possible for our immune system to distinguish ‘self’ from ‘not-self.’ If this process is disrupted, the body can end up attacking itself.”

The researchers were excited by this finding because SIAE has recently been linked to autoimmune diseases like rheumatoid arthritis and type I diabetes.

“Prior to this research, we knew that there was an autoimmune cascade effect with preeclampsia, but we didn’t know where it originated,” Dr. Piedrahita adds. “Now we know that disregulation of SIAE helps start the cascade. We’ve been able to fill in the blanks, and hopefully pregnant women and their babies will benefit as a result.”

The research was funded by a grant from the National Institutes of Health. The Department of Molecular Biomedical Sciences and the Center for Comparative Medicine and Translational Research are part of NC State’s College of Veterinary Medicine.

The Center for Comparative Medicine and Translational Research (CCMTR) is a community of more than 100 scientists from five NC State colleges. These investigators are involved in collaborative ”One Health” studies with government, private, and other academic researchers to advance knowledge and practical applications that improve the health of animals and humans.

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An abstract of the paper follows.

“Transcriptional profiling of human placentas from pregnancies complicated by preeclampsia reveals disregulation of sialic acid acetylesterase and immune signalling pathways”

Authors:  J.A. Piedrahita, S. Tsai, N.E. Hardison, A.A. Motsinger-Reif, S.R. Bischoff , North Carolina State University; B.H. Thames, A.H. James, Duke University School of Medicine

Published: February, 2011 in Placenta

Abstract:  The placenta plays an important role as a regulator of fetal nutrition and growth throughout development and placental factors contribute to gestational abnormalities such as preeclampsia. This study describes the genome-wide gene expression profiles of a large (n ¼ 60) set of human placentas in order to uncover gene expression patterns associated with preeclampsia. In addition to confirming changes in expression of soluble factors associated with preeclampsia such as sFLT1 (soluble fms-like tyrosine kinase-1), sENG (soluble endoglin), and INHA (inhibin alpha), we also find changes in immune-associated signaling pathways, offering a potential upstream explanation for the shallow trophoblast invasion and inadequate uterine remodeling typically observed in pathogenesis of preeclampsia. Notably, we also find evidence of preeclampsia-associated placental upregulation of sialic acid acetylesterase (SIAE), a gene functionally associated with autoimmune diseases.

Posted Feb. 10, 2011