Maternal inflammation disrupts transplacental antibody transfer in pregnant individuals with and without HIV

Abstract

Introduction: Maternally transferred immunity plays a critical role in protecting infants from pathogens during the vulnerable period before their own immune system matures. Maternal IgG antibodies cross the placenta and circulate in the infant's body for up to six months, providing protection against infection. Despite the importance of transplacental antibody transfer, the mechanisms regulating this process remain poorly understood, including the maternal and placental factors that influence transfer efficiency. Methods: We analyzed maternal and umbilical cord plasma samples from 354 mother-baby dyads in Uganda, of whom 176 were pregnant individuals with HIV taking antiretroviral therapy. We measured IgG antibody levels, antibody binding to Fc receptors, antibody glycosylation, and cytokine levels in both maternal and umbilical cord compartments, and we evaluated placental inflammatory states with placental histology. We used this comprehensive dataset to define correlations between transplacental antibody transfer efficiency, placental inflammation, and cytokine levels in maternal and umbilical cord plasma. Results: We found that antibody transfer efficiency was not impacted by histologic placental inflammation, but that higher maternal plasma levels of the pro-inflammatory cytokines TNF-α and IL-6 correlated with reduced transplacental antibody transfer efficiency. Discussion: Our findings reveal the impact of maternal systemic inflammation on antibody transfer across the placenta and have implications for maternal immunization strategies.