Fc Characteristics Mediate Selective Placental Transfer of IgG in HIV-Infected Women

Cell. 2019 Jun 27;178(1):190-201.e11. doi: 10.1016/j.cell.2019.05.046. Epub 2019 Jun 13.

Abstract

The placental transfer of maternal IgG is critical for infant protection against infectious pathogens. However, factors that modulate the placental transfer of IgG remain largely undefined. HIV-infected women have impaired placental IgG transfer, presenting a unique "disruption model" to define factors that modulate placental IgG transfer. We measured the placental transfer efficiency of maternal HIV and pathogen-specific IgG in US and Malawian HIV-infected mothers and their HIV-exposed uninfected and infected infants. We examined the role of maternal HIV disease progression, infant factors, placental Fc receptor expression, IgG subclass, and glycan signatures and their association with placental IgG transfer efficiency. Maternal IgG characteristics, such as binding to placentally expressed Fc receptors FcγRIIa and FcγRIIIa, and Fc region glycan profiles were associated with placental IgG transfer efficiency. Our findings suggest that Fc region characteristics modulate the selective placental transfer of IgG, with implications for maternal vaccine design and infant health.

Keywords: HIV; IgG Fc region; antibodies; infant protection; maternal immunity; placental IgG transfer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Disease Progression
  • Female
  • Glycosylation
  • HIV / genetics*
  • HIV Infections / immunology
  • HIV Infections / transmission*
  • HIV Infections / virology
  • Humans
  • Immunoglobulin Fc Fragments / metabolism
  • Immunoglobulin G / blood*
  • Infant
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical*
  • Malawi
  • Placenta / metabolism*
  • Pregnancy
  • Pregnancy Complications, Infectious / immunology
  • Pregnancy Complications, Infectious / virology*
  • Receptors, IgG / metabolism*
  • United States
  • Viral Load / genetics

Substances

  • FCGR3A protein, human
  • Fc gamma receptor IIA
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Receptors, IgG