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

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

Author information

1
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
2
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
3
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
4
Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, NC 27607, USA.
5
Ragon Institute of the Massachusetts General Hospital, MIT and Harvard, Cambridge, MA 02139, USA.
6
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
7
Department of Epidemiology, Harvard T.H. School of Public Health, Boston, MA 02115, USA.
8
Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, NC 27607, USA; Bioinformatics Graduate Program, North Carolina State University, Raleigh, NC 27607, USA; Bioinformatics Research Center, North Carolina State University, Raleigh, NC 27607, USA.
9
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA; Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: genevieve.fouda@duke.edu.
10
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA; Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: sallie.permar@duke.edu.

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

PMID:
31204101
DOI:
10.1016/j.cell.2019.05.046

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