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Update on transplacental transfer of IgG Subclasses: Impact of maternal and fetal factors

Update on transplacental transfer of IgG Subclasses: Impact of maternal and fetal factors
Update on transplacental transfer of IgG Subclasses: Impact of maternal and fetal factors
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.
IgG, antibody, immunology, infection, maternal vaccination, neonatal, placenta, pregnancy
1664-3224
Clements, Toby
ab39a386-8f92-4be3-b87d-0d14cd207f46
Rice, Thomas
0290b485-fed4-4641-8dd9-1f4e3a694d3e
Vamvakas, George
d62ca48a-92a9-4293-8e16-492f3a2325b3
Barnett, Sara
b73a30a0-0d68-4542-b03d-3311313d9a76
Barnes, Megan
4f9392f3-8918-44c5-8586-7c9d40147e43
Donaldson, Beverly
90280728-49aa-4644-810a-5fcf7611df8c
Jones, Christine E
48229079-8b58-4dcb-8374-d9481fe7b426
Kampmann, Beate
8aab20a5-1787-45f5-b51f-15ef86706500
Holder, Beth
7be76194-2813-4e5a-b0d4-9f34511c7799
Clements, Toby
ab39a386-8f92-4be3-b87d-0d14cd207f46
Rice, Thomas
0290b485-fed4-4641-8dd9-1f4e3a694d3e
Vamvakas, George
d62ca48a-92a9-4293-8e16-492f3a2325b3
Barnett, Sara
b73a30a0-0d68-4542-b03d-3311313d9a76
Barnes, Megan
4f9392f3-8918-44c5-8586-7c9d40147e43
Donaldson, Beverly
90280728-49aa-4644-810a-5fcf7611df8c
Jones, Christine E
48229079-8b58-4dcb-8374-d9481fe7b426
Kampmann, Beate
8aab20a5-1787-45f5-b51f-15ef86706500
Holder, Beth
7be76194-2813-4e5a-b0d4-9f34511c7799

Clements, Toby, Rice, Thomas, Vamvakas, George, Barnett, Sara, Barnes, Megan, Donaldson, Beverly, Jones, Christine E, Kampmann, Beate and Holder, Beth (2020) Update on transplacental transfer of IgG Subclasses: Impact of maternal and fetal factors. Frontiers in Immunology, 11, [1920]. (doi:10.3389/fimmu.2020.01920).

Record type: 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.

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More information

Accepted/In Press date: 16 July 2020
e-pub ahead of print date: 11 September 2020
Keywords: IgG, antibody, immunology, infection, maternal vaccination, neonatal, placenta, pregnancy

Identifiers

Local EPrints ID: 443974
URI: http://eprints.soton.ac.uk/id/eprint/443974
ISSN: 1664-3224
PURE UUID: 9830a8ac-2b40-4a52-83f8-64c58b85cdfc
ORCID for Christine E Jones: ORCID iD orcid.org/0000-0003-1523-2368

Catalogue record

Date deposited: 18 Sep 2020 16:31
Last modified: 28 Apr 2022 02:18

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Contributors

Author: Toby Clements
Author: Thomas Rice
Author: George Vamvakas
Author: Sara Barnett
Author: Megan Barnes
Author: Beverly Donaldson
Author: Beate Kampmann
Author: Beth Holder

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