Immune Profiling Identifies Early Maternal Autoantibodies Linked to Preterm Birth Risk

Preterm birth is the leading cause of newborn death worldwide, yet its underlying causes and which pregnancies are most at risk remain difficult to determine. Helping to clarify this risk, new findings suggest that specific maternal antibodies may be associated with delivery before 37 weeks of gestation.

Researchers at UC San Francisco (UCSF) used a new immune profiling tool to identify antibodies that appeared earlier and at higher levels during pregnancy in women who later delivered preterm. The technology, called PhIP-Seq, broadly profiles antibodies in blood and identifies the proteins they recognize, including the body’s own proteins. In this study, it was used to detect antibodies that emerged consistently after pregnancy began.

The team first recruited volunteers at UCSF’s fertility clinic, collected baseline blood samples, and followed a small group of women after frozen embryo transfer. The analysis was then expanded to blood samples from more than 2,000 pregnant women across eight cohorts, including specimens collected at 15 weeks of gestation through California’s statewide prenatal screening program. The larger dataset showed that women who later delivered prematurely developed broader antibody changes earlier in pregnancy than women who delivered at term.

One antibody targeted interleukin-1 receptor antagonist (IL-1RA), a protein that normally limits inflammation by blocking interleukin-1 beta (IL-1β). When this antibody neutralizes IL-1RA, it removes a natural brake on IL-1β-driven inflammation, which is associated with uterine contractions. In pregnant mice injected with IL-1RA antibodies, maternal blood levels of IL-1β increased and placentas developed damage resembling changes seen in human preterm delivery. 

The study, “Evidence for Maternal Autoantibodies in the Pathogenesis of Preterm Birth,” was published in Nature Immunology on October 14, 2026.

The researchers noted that anti-IL-1RA antibodies were found in only a fraction of preterm births, indicating that other causes are likely involved. They also do not yet know whether the antibodies were present before pregnancy or appeared after conception. 

“We built our tool to find exactly these kinds of hidden immune signals,” said Joe DeRisi, the Gordon M. Tomkins professor of biochemistry and biophysics at UCSF. “The fact that it's pointing us toward why some pregnancies go wrong is an exciting result.”

“We wanted to capture the immune system before pregnancy, and then measure what changed. This patient population was particularly well suited to answering that question, because the timing of pregnancy following a frozen embryo transfer could be closely tracked,” said Elze Rackaityte, assistant professor at UCSF.

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