Blocking the neonatal Fc receptor (FcRn) has been shown to reduce the risk of serious complications in hemolytic disease of the fetus and newborn (HDFN), according to a review published recently in BioDrugs.
This review highlights the potential of FcRn antagonists like nipocalimab to prevent dangerous levels of maternal antibodiesAntibody A protein made by the immune system that recognizes and attacks foreign substances, such as bacteria, or in HDFN, fetal red blood cells carrying incompatible antigens. from harming developing babies.
Nipocalimab works by lowering the amount of maternal IgG, a type of antibodyAntibody A protein made by the immune system that recognizes and attacks foreign substances, such as bacteria, or in HDFN, fetal red blood cells carrying incompatible antigens. that, in HDFN, mistakenly attacks fetal red blood cells. This attack happens when maternal IgG crosses the placenta using the FcRn pathway. Clinical trials have shown that giving nipocalimab starting between weeks 14 and 35 of pregnancy significantly improves outcomes. A phase 3 trial is underway to explore earlier use, beginning at week 13.
“In hemolytic disease of the fetus and newborn (HDFN; also called erythroblastosis fetalisErythroblastosis fetalis An older term for HDFN, describing the severe destruction of fetal red blood cells caused by maternal antibodies.), the fetus has inherited paternal blood groupBlood group A classification of blood based on inherited markers found on red blood cells. The ABO and Rh blood groups are most common in HDFN. factors (RhRh factor A protein or antigen found on red blood cells. When an Rh-negative mother carries an Rh-positive fetus, her immune system may make antibodies that attack the fetus' red blood cells. and/or ABO) that differ from those of the mother-to-be,” explained the authors of this review. They continued, “While such a blood type mismatch is not uncommon, it can result in alloimmunizationAlloimmunization When a person’s immune system develops antibodies against foreign antigens from the same species—such as when an Rh-negative mother’s body forms antibodies against her baby’s Rh-positive red blood cells. when combined with fetal-maternal bleeding, which occurs in around 5% of pregnancies and increases throughout the gestation period.”
HDFN occurs when a pregnant person’s immune system creates antibodies against proteins inherited from the baby’s father. This immune reaction is often triggered by fetal-maternal bleeding, which happens in about 5 percent of pregnancies. These antibodies, especially the IgG1 and IgG3 types, are highly destructive and can lead to life-threatening anemiaAnemia A condition that occurs when the body doesn’t have enough healthy red blood cells to carry oxygen to its tissues. In HDFN, anemia occurs when maternal antibodies destroy fetal red blood cells., fluid buildup (hydrops fetalisHydrops fetalis A serious, sometimes fatal condition in which fluid builds up in a baby’s tissues and organs due to severe anemia from HDFN.), or even fetal death. While rare—affecting 3 to 80 out of every 100,000 pregnancies—HDFN can have devastating effects.
Read more about HDFN prognosis
The most common target of these harmful antibodies is the RhD antigen, although Kell antigensAntibody A protein made by the immune system that recognizes and attacks foreign substances, such as bacteria, or in HDFN, fetal red blood cells carrying incompatible antigens. are also associated with poor fetal outcomes. Nipocalimab, first developed by Momenta Pharmaceuticals and now owned by Johnson & Johnson, is the first FcRn blocker tested in pregnant patients. The drug has been granted a rare pediatric disease designation by the U.S. Food and Drug Administration (FDA) for HDFN.
Unlike treatments that suppress the entire immune system, FcRn inhibitors work by speeding up the breakdown of IgG antibodies without broadly weakening immunity. This targeted approach has also shown promise in treating other pregnancy-related autoimmune diseases, like fetal and neonatal immune thrombocytopenia, and may benefit common conditions such as rheumatoid arthritis.
As more FcRn-based therapies are developed, experts believe this class of drugs could transform how doctors manage both rare and widespread autoimmune conditions.
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