Study identifies antibody pattern linked to miscarriage

Stephen Elledge, PhD

During pregnancy, the immune system is charged with a difficult task: Be vigilant enough to protect against infection, yet tolerant enough to allow the developing fetus to grow, even though it has genetic differences from the mother.

Important immune changes occur that may support this balance, including changes in maternal antibodies, but little is known about how pregnancy affects the specific targets of these antibodies. 

In a new study, researchers from Mass General Brigham and the Howard Hughes Medical Institute, led by Brandon Sie, PhD, under the supervision of Stephen Elledge, PhD, investigated how pregnancy reshapes the maternal antibody repertoire and identified an unusual pattern of IgA antibodies that may appear shortly before miscarriage. 

They found that although overall concentrations of maternal antibodies decreased during pregnancy, the diversity of targets recognized by IgG and IgA antibodies expanded.

In pregnancies that ended in miscarriage, they also observed sharp increases in IgA antibodies against certain viral and human proteins shortly before pregnancy loss. This pattern, which they called “IgA STORM,” identified 14 out of 19, or about 74% of miscarriages in the study. 

While the findings offer new insight into how maternal immunity changes during pregnancy, larger studies are needed to determine whether these antibody patterns could help identify pregnancies at risk or even explain how some miscarriages occur. 

Published in Cell Reports Medicine on Sept. 15, 2026 | Read the paper “Humoral pregnancy analyses reveal strategies for fetal protection and aberrancy in miscarriage” 

Summary reviewed by: Stephen Elledge, PhD, senior author