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The study reveals early molecular signs of high risk pregnancy



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Women who have healthy pregnancies tend to show clear changes in the activities of immune genes that begin at the beginning of pregnancy, while women who have complicated pregnancies tend to show clear consequences of that pattern, according to a new study from a team led by Weill researchers Cornell. Medicine and Hospital of Special Surgery (HSS).

The study, published on April 8th in Journal of Experimental Medicine, was designed to find early molecular predictors of preeclampsia hypertension syndrome, involuntary abortion and other adverse pregnancy outcomes in women with autoimmune lupus disorder, who face a relatively high risk of such outcomes. More than half of the more than 200 women studied were patients with lupus. But the results suggest that modulation of the immune system during pregnancy is very similar in women with or without lupus.

"These discoveries help us to understand not only pregnancy for women with lupus without pregnancy in general," said study author Dr Virginia Pascual, director of Drukier do Gale and Ira Drukier Institute for children's health and paediatrician professor Ronay Menschel in Weill Cornell Medicine. Dr. Pascual received a research scholarship and an honorary consultant from Sanofi-Pasteur.

"There are implications here to predict the negative results of pregnancy and also to identify therapeutic targets to prevent these results," said Dr. Jane Salmon, professor of medicine and medicine at obstetrics and gynecology at Weill Cornell Medicine and Collette Kean, a research professor at the HSS. Dr. Salmon received a grant initiated by UCB Pharmaceuticals researchers.

Lupus affects more than 500,000 people in the United States and about 90 percent are women. The disorder presents attacks of antibodies and other immune elements in the skin, heart, kidneys and other organs. Women with pregnant lupus have an approximate probability of 20 percent of serious complications, including spontaneous abortion, premature delivery, the birth of dead and pre-eclampsia, a condition that endangers both the mother and the fetus. Previous investigations suggest that such complications, even in women without lupus, are at least partly caused by inadequate regulation of the maternal immune system – which should be tamed during pregnancy to allow the tolerance of fetal tissue in part "foreigner".

As of 2003 and for over a decade later, Dr. Salmon and colleagues recorded more than 700 women, about half of them pregnant with lupus, for a multicenter study called PROMISSE designed to detect risk factors for adverse pregnancy outcomes. For the new study, doctors. Salmon and Pascual and their colleagues used blood samples and other clinical data from a subgroup of the cohort enrolled in 2003-13, including 92 pregnant women who had lupus and 43 pregnant women who had no disorder.

The analysis of the patterns of gene activity in the white blood cells of these women during the course of pregnancy showed that in healthy women with uncomplicated pregnancies, the key elements of the immune system tend to calm down shortly after the establishment of pregnancy and tended to remain relatively calm at long pregnancy These were largely the same sets of genes that are hyperactive in lupus, and include genes related to the production of molecules called type I interferons that streamline an immune response to viral infections.

"The surprise for us was when we analyzed the data of women with lupus who had pregnancies without complications," said Dr. Pascual. "They started, as expected, with a higher level of activity in these immune pathways, but once they became pregnant these immunological pathways were greatly modulated as pregnant women without lupus."

On the contrary, in pregnant women who developed preeclampsia or other serious complications, these immunological pathways were reduced to a lesser extent from their basal levels or nothing.

In a separate study of 25 healthy women undergoing in vitro fertilization, researchers observed the same sign of immune gene from pregnancy and complicated pregnancy and found that these patterns began to emerge at the beginning of pregnancy, with the implantation of the embryo.

The results, if confirmed in larger groups of pregnant women, could lead to the development of early diagnosis tests to predict the complications of pregnancy and, ultimately, treatments that calm specific elements of the immune system to protect women from the complications. "If we could identify a route of destination with drugs to prevent preeclampsia in patients with lupus," said Dr. Salmon, "we could immediately consider the same treatment approach to protect women who do not have lupus but who have similar high risk biomarkers no pregnancy. "

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