Fetal immune rejection may cause preterm labor: study

WASHINGTON, April 25 (Xinhua) -- American scientists identified one inducing factor for preterm labor, a common pregnancy complication: the fetal immune system "wakes up" too early and begins to reject the mother, causing the uterus to start contracting.

A study published on Wednesday in the journal Science Translational Medicine, showed the fetal immune system became triggered in a case of mistaken identity. An initial infection in the mother could result in inflammation and arouse the fetal immune system.

The fetal immune cells confuse the mother's cells for an invader and mount an attack, in the form of inflammatory chemicals and these chemicals then trigger contractions, leading to preterm labor, the leading cause of infant mortality, according to the researchers.

The paper's senior author Tippi MacKenzie, associate professor in the University of California San Francisco's Division of Pediatric Surgery and the Fetal Treatment Center, said the finding contradicted the dogma that the fetus had a very immature immune system, and as a result, people hadn't really considered its possible role in pregnancy complications.

The researchers tested umbilical cord blood, which contains fetal cells, along with blood taken from 89 women who had healthy pregnancies and 70 who went into early labor.

While the scientists saw no signs of an immune response in the mother's blood, they detected activation in two types of immune cells in the cord blood of preterm infants.

Just as in an organ transplant, the immune systems of the mother and the fetus have to tolerate one another, so the fetus is not rejected. This tolerance is governed by immune cells known as regulatory T cells, which dampen the immune system by keeping the other types of T cells in check.

However, during preterm labor the infant's immune system was found to be activated specifically to attack the mother's cells. The researchers detected higher levels of both dendritic cells and effector T cells in the cord blood of preterm infants.

Dendritic cells present foreign substances to the T cells to signify that they are a potential threat, and T cells, the primary fighter cells of the immune system, then mount an attack by releasing inflammatory chemicals, according to the researchers.

The researchers found that T cells from preterm infants made significantly higher levels of inflammatory chemicals and interferon gamma than those from full-term infants.

In a laboratory model of uterine contraction, the researchers discovered that these chemicals induced contraction of uterine cells.

"The medicines we use to treat preterm labor right now are just aimed at stopping the uterus from contracting. But at that point, the horse is out of the barn," MacKenzie said. "What we really have to do is diagnose and treat fetal immune activation, which is probably starting weeks before the patient comes in with the uterine contractions."

MacKenzie's lab is now pursuing biomarkers in the mother's blood that can identify whether the fetal immune system is activated and increasing risk for preterm labor. Enditem