Maternal IGHG locus duplications impair infants’ passive immunity

Infants depend on passive immunity to safeguard them against infections during the first months of life. Maternal immunoglobulin G (IgG) antibodies are actively transported across the placenta and confer this protection. In this study, we discovered common, but previously unrecognized, naturally occurring gene fusions between loci encoding IgG1 and IgG4 subclasses that impair the transplacental IgG transport. These gene fusions result from gene duplications combining regulatory elements of the Immunoglobulin Heavy Constant Gamma ( IGHG1) gene with IGHG4 -like constant regions. Mothers with these duplications generate antibodies that are less efficiently transferred to the fetus, resulting in lower antibody levels in newborns and a higher risk of respiratory infections during infancy. Our insights warrant consideration in the development of personalized vaccination strategies during pregnancy to better protect infants against infectious diseases.