Researchers at UC San Francisco have discovered maternal autoantibodies targeting the inflammation-controlling protein IL-1RA, which appear earlier and at higher levels in women experiencing preterm births. Published in Nature Immunology, the discovery utilizes a new UCSF immune profiling tool and PhIP-Seq technology to screen for preterm birth risk and potential interventions.
UC San Francisco Researchers Study Global Preterm Birth Rates
A typical human pregnancy lasts 40 weeks, but approximately 1 in 10 pregnant women experience labor starting too soon. According to researchers at UC San Francisco, premature or preterm birth remains the leading cause of newborn deaths worldwide. Despite its severity, doctors have historically struggled to understand why early labor occurs or how to predict which pregnancies face the highest risk.
Joe DeRisi and Elze Rackaityte Recruitment of Fertility Clinic Volunteers
To investigate whether the maternal immune system triggers certain cases of preterm births, a team led by Joe DeRisi—the Gordon M. Tomkins Professor of Biochemistry and Biophysics at UCSF—and Elze Rackaityte recruited volunteers from a UCSF fertility clinic. The researchers collected initial blood samples and tracked a subset of women who became pregnant through frozen embryo transfers, allowing them to capture immune system baselines before conception and measure subsequent changes.
PhIP-Seq Technology and the Preterm Birth Signature.
The research team employed a refined technology called PhIP-Seq to examine antibodies in the blood and identify which proteins they recognize, including reactions against the body’s own proteins. After establishing a baseline of antibodies that consistently appear once pregnancy begins, the team analyzed blood samples from over 2,000 pregnant women across eight cohorts. These included samples gathered at 15 weeks of gestation by California’s statewide prenatal screening program.
The data revealed that women who delivered prematurely experienced broader antibody changes earlier than those who delivered at term. Within this signature, a specific antibody stood out by reacting against IL-1RA, a protein responsible for controlling inflammation in the body. IL-1RA operates by blocking IL-1β, a molecule that drives inflammation known to trigger uterine contractions. By neutralizing IL-1RA, the antibody removes the body’s natural brake, allowing IL-1β and inflammation to rise unchecked.
Animal Testing and Potential Treatment Pathways.
To confirm the significance of these findings, Rackaityte injected the IL-1RA antibodies into pregnant mice. The injections caused IL-1β levels to rise in the mothers’ blood and produced placental damage mirroring human preterm deliveries. Examining human placental tissue, Rackaityte discovered that IL-1RA normally accumulates in the junctions between cells lining placental blood vessels where oxygen and nutrients pass from mother to fetus.
Anakinra Application for Rheumatoid Arthritis and Inflammatory Diseases
The newly published findings suggest that Anakinra—a synthetic form of the IL-1RA molecule utilized for nearly two decades to treat inflammatory diseases such as rheumatoid arthritis—could be investigated as a method to prevent preterm births. The intervention aims to put the brakes back on IL-1, thereby preventing inflammation and preterm uterine contractions.
Researchers emphasize that anti-IL-1RA antibodies appeared in only a fraction of preterm births, indicating the presence of other causes. Scientists do not yet know whether the antibodies existed prior to pregnancy due to previous infections or immune diseases, or if they developed after conception.
