See How the Immune Systems of the Mom and Her Fetus Interact to Prevent or Trigger Premature Birth

Is premature birth triggered by rejection of the mother by the fetus’ immune system? Or a rejection of the fetus by the mother’s immune system? Or both? Two new studies explore the question and turn up a startling new discovery in the process.

Most spontaneous preterm births (SPB) can be traced to infection or inflammation in the mother. This disturbance triggers a cascade of reactions that ultimately leads to uterine contractions and the onset of preterm labor. But recently, two scientists—one a clinician and the other researcher, both funded in part by March of Dimes, but working one opposite ends of the problem—have turned up some surprising findings about the role immune systems play in initiating premature birth.

Common wisdom, debunked

Until now, the common wisdom dismissed the idea that those too-early contractions could be caused by the fetal immune system because it was thought too immature to play much of a role. A new study entitled, “T cell activation and the breakdown of maternal-fetal tolerance in preterm labor,” and recently published in Science Translational Medicine proves otherwise. It shows that inflammation or infection in the mother, awakens the fetus’ immune system to attack the mother’s cells by secreting inflammatory chemicals of its own that trigger uterine contractions, initiating premature labor.

Principal investigator, senior author, and former March of Dimes double grantee, Tippi MacKenzie, MD, and associate professor in the UCSF Division of Pediatric Surgery and the Fetal Treatment Center pointed out that the outsized reaction of the fetal immune system was similar to the reactions triggered in organ transplants. “Just as in an immune system’s rejection of transplanted organs, the fetal immune system mobilized T-cells and dendrite to attack the mother cells,” said Dr. MacKenzie, “which is obviously a case of mistaken identity, but the same sort of reaction we might expect in a hostile uterine environment.”

Validation by Complementory Findings

These results have been validated and complemented by another new study showing a similar, but opposite reaction by the mother’s immune system. This study utilized data housed in the March of Dimes Data Repository for Prematurity Research, Prematurity Research Center at Stanford University School of Medicine. Created by Data Repository leader, Marina Sirota, Ph.D., and study first author Bianca Vora, Ph.D. Candidate, University of California, San Francisco. it looked for any transcriptomic biomarkers on the maternal side that might be predictive of preterm birth.

“We started agnostically, but arrived in the same area, and the same reason for preterm birth, the role of the immune system,” said Professor Sirota. “While we also saw the fetal immune system at work, we also observed the opposite effect between the maternal and the fetal immune systems and the way that they might interact, which is very complimentary to Dr. MacKenzie’s work.”

Turning up the surprising relationship between the two immune systems creates a promising new vector that is both complementary and original in the exploration of the causes and ultimately the cure for premature birth. And the result of March of Dimes sponsored Transdisciplinary Research at its best.

Download Prematurity Research Centers 2018 Q2 Update