A pregnancy typically lasts 40 weeks, but for about 1 in 10 women, labor begins prematurely. Premature or preterm birth remains the leading cause of newborn deaths worldwide. Doctors have long sought to understand its origins and identify which pregnancies face the highest risk. Now, a team at UC San Francisco has uncovered antibodies that may trigger early labor. These antibodies appeared in raised levels and emerged earlier in pregnancies that resulted in births before 37 weeks, compared to those delivering at term.
New Tool Unlocks Immune Origins of Preterm Birth
The findings were published in Nature Immunology and relied on a new immune profiling tool developed at UCSF. This work could lead to both improved screening methods for preterm birth risk and potential interventions to prevent it. Tomkins professor of biochemistry and biophysics at UCSF and senior author of the study.
Every pregnancy challenges the human immune system, as the fetus carries different genetics than the mother. Normally, the immune system avoids attacking the developing child. DeRisi’s team suspected that immune responses might contribute to some preterm births. To investigate, they recruited volunteers from UCSF’s fertility clinic, collecting initial blood samples and later tracking a subset of women after they became pregnant through frozen embryo transfers.
The researchers used a refined technique called PhIP-Seq, which maps antibodies in blood and identifies which proteins they target—including reactions to the body’s own proteins. Applying this method, they detected a set of antibodies that consistently emerged once pregnancy began. With this baseline established, they analyzed a larger dataset: blood samples from over 2,000 pregnant women across eight cohorts, including specimens collected by California’s statewide prenatal screening program at 15 weeks of gestation. This allowed them to determine whether any antibodies were specifically linked to preterm birth rather than pregnancy itself.
The data revealed that women who delivered prematurely exhibited broader antibody changes earlier than those who carried pregnancies to term. Among these, one antibody stood out: it targeted IL-1RA, a protein that regulates inflammation. IL-1RA blocks IL-1β, a molecule known to provoke uterine contractions. When antibodies neutralize IL-1RA, the inflammatory brake fails, allowing IL-1β to drive unchecked inflammation—a potential trigger for preterm labor.
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Mice Study Shows Antibodies Can Trigger Early Labor
To test this, Rackaityte injected the IL-1RA antibodies into pregnant mice. The mothers’ IL-1β levels rose, and their placentas showed damage similar to that observed in human preterm deliveries. She then examined human placental tissue to locate IL-1RA. It accumulated in the junctions of cells lining placental blood vessels, where nutrients and oxygen transfer from mother to fetus.
The placenta appears to stockpile IL-1RA to protect the pregnancy, depositing it along blood vessels. Given that Anakinra, a synthetic version of IL-1RA, has treated inflammatory diseases like rheumatoid arthritis for nearly two decades, the findings suggest it could be repurposed to prevent preterm births by restoring the inflammatory brake.
Future Research Aims to Find More Triggers and Solutions
The team acknowledges that anti-IL-1RA antibodies were found in only a fraction of preterm cases, indicating other causes likely exist. They also do not yet know whether these antibodies predate pregnancy, perhaps triggered by prior infections or immune disorders, or arise after conception. The women in the study were only monitored after pregnancy began, leaving this question unanswered.
In her new lab, Rackaityte will continue studying anti-IL-1RA antibodies and explore additional antibodies linked to the preterm-birth immune signature. This work could clarify the immune system’s broader role in pregnancy complications and improve medical care.