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Fc 特征介导 HIV 感染女性 IgG 的选择性胎盘转移。

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

机构信息

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.

Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

出版信息

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.

摘要

母体 IgG 向胎盘的转移对于婴儿免受感染性病原体的侵害至关重要。然而,调节 IgG 向胎盘转移的因素在很大程度上仍未得到明确。感染 HIV 的妇女存在胎盘 IgG 转移受损的情况,这为定义调节胎盘 IgG 转移的因素提供了一个独特的“破坏模型”。我们测量了美国和马拉维感染 HIV 的母亲及其 HIV 暴露的未感染和感染婴儿的母体 HIV 和病原体特异性 IgG 的胎盘转移效率。我们研究了母体 HIV 疾病进展、婴儿因素、胎盘 Fc 受体表达、IgG 亚类和聚糖特征及其与胎盘 IgG 转移效率的关系。母体 IgG 的特征,如与胎盘表达的 Fc 受体 FcγRIIa 和 FcγRIIIa 的结合,以及 Fc 区聚糖特征与胎盘 IgG 转移效率相关。我们的研究结果表明,Fc 区特征调节 IgG 的选择性胎盘转移,这对母体疫苗设计和婴儿健康具有重要意义。

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