Update on trans-placental transfer of IgG subclasses: impact of maternal and fetal factors
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Author(s)
Type
Journal Article
Abstract
Transplacental antibody transfer from mother to fetus provides protection from infection in the first weeks of life, and the four different subclasses of IgG (IgG1, IgG2, IgG3, and IgG4) have diverse roles in protection against infection. In this study, we evaluated concentrations and transplacental transfer ratios of the IgG subclasses in a healthy UK-based cohort of mother-cord pairs, and investigated associations with maternal, obstetric, and fetal factors. In agreement with previous studies, we found a strong association between maternal and cord IgG for all subclasses. We report a transfer efficiency hierarchy of IgG1>IgG3>IgG4=IgG2 in our study population, and our review of the literature demonstrates that there is no consensus in the hierarchy of subclass transfer, despite the commonly made statement that the order is IgG1>IgG4>IgG3>IgG2. We report additional data regarding negative associations between elevated maternal IgG concentrations and maternal/cord transfer ratios, finding an effect on IgG1, IgG2, and IgG3 subclasses. Levels of IgG subclasses were the same between venous and arterial blood samples from the umbilical cord, but there was a significantly higher level of total IgG in arterial blood. We found no correlation between placental FcRn protein levels and IgG transfer in our cohort, suggesting that IgG is the main determinant of observed differences in transplacental transfer ratios at term. Neonatal IgG1 and IgG4 levels were increased with later gestation at delivery, independent of any increase in transplacental transfer, indicating that the benefit of later gestation is through accumulation of these subclasses in the fetus. Neonatal IgG2 levels and transfer ratios were reduced in rhesus-negative pregnancies, suggesting that administered anti-D antibodies may compete for transplacental transfer of this subclass. Maternal influenza vaccination resulted in elevated maternal and neonatal levels of IgG4, whereas maternal Tdap vaccination had no impact on neonatal levels of the subclasses, nor transfer. However, within Tdap vaccinated pregnancies, later gestation at Tdap vaccination was associated with higher transplacental transfer. Our study provides information regarding levels and transfer of IgG subclasses in healthy term pregnancies and demonstrates the importance of recording detailed clinical information in studies of antibody transfer, including parity, ethnicity, and timing of maternal vaccine delivery.
Date Issued
2020-09-11
Date Acceptance
2020-07-16
Citation
Frontiers in Immunology, 2020, 11, pp.1-17
ISSN
1664-3224
Publisher
Frontiers Media
Start Page
1
End Page
17
Journal / Book Title
Frontiers in Immunology
Volume
11
Copyright Statement
© 2020 Clements, Rice, Vamvakas, Barnett, Barnes, Donaldson, Jones, Kampmann and Holder. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
License URL
Sponsor
NIHR Imperial BRC
NIHR Imperial BRC
IMPRINT network
IMPRINT network
Medical Research Council (MRC)
Identifier
https://www.frontiersin.org/articles/10.3389/fimmu.2020.01920/full#h1
Grant Number
P72781
ITCR079012
Subjects
1107 Immunology
1108 Medical Microbiology
Publication Status
Published
Article Number
1920
Date Publish Online
2020-09-11