San Francisco - In what was hailed as the first-ever characterization of the meticulously timed immune system changes in women that occur during pregnancy, researchers at the Stanford University School of Medicine have revealed that there is an immune clock of pregnancy.
"Pregnancy is a unique immunological state," said Brice Gaudilliere, assistant professor of anesthesiology, perioperative and pain medicine and senior author of the study published in Science Immunology.
"We found that the timing of immune system changes follows a precise and predictable pattern in normal pregnancy."
Physicians have long known that the expectant mother's immune system adjusts to prevent her body from rejecting the fetus, but no one had investigated the full scope of these changes, nor asked if their timing was tightly controlled.
The new research aimed to understand why preterm births happen and how they could be prevented. Nearly 10 percent of US infants arrive three or more weeks early.
The study used blood samples collected from 18 women who had full-term pregnancies. Each woman gave four blood samples - one during each of the three trimesters of pregnancy and one six weeks after delivery. Samples from an additional group of 10 women with full-term pregnancies were used to validate the findings.
By using mass cytometry to simultaneously measure up to 50 properties of each immune cell in the blood samples, the researchers counted the types of immune cells, assessed what signaling pathways were most active in each cell, and determined how the cells reacted to being stimulated with compounds that mimic infection with viruses and bacteria.
With an advanced statistical modeling technique, they then described in detail how the immune system changes throughout pregnancy. The study confirmed immune features of pregnancy that were already known.
In addition, the researchers uncovered several previously unappreciated features of how the immune system changes, such as the finding that activity of the signal transducer and activator of transcription 5, or STAT5, signaling pathway in CD4+T cells progressively increases throughout pregnancy on a precise schedule, ultimately reaching levels much higher than in nonpregnant individuals. The STAT5 pathway is involved in helping another group of immune cells, regulatory T cells, to differentiate.
The next step of the research will be to conduct similar research using blood samples from women who deliver their babies prematurely to see where their trajectories of immune function differ from normal.
"We're especially interested in understanding more precisely what is happening very early and very late in pregnancy," Gaudilliere was quoted as saying in a news release. "We'd like to see if there is really a switch we can catch, a sweet spot where deviation from the norm would be maximal with pathology."