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Transfusion. 2014 Mar;54(3):665-71. doi: 10.1111/trf.12334. Epub 2013 Jul 7.

H435-containing immunoglobulin G3 allotypes are transported efficiently across the human placenta: implications for alloantibody-mediated diseases of the newborn.

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1
Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, China; Leiden University Medical Center, Leiden, The Netherlands.

Abstract

BACKGROUND:

The neonatal receptor (FcRn) extends the half-life of human immunoglobulin (Ig)G and transports it across the placenta, providing the newborn with humoral immunity. Of the four subclasses, IgG3 stands out with strong effector functions, short half-life (7 days vs. 21 days for other subclasses), and poor placental transport. We recently described how a single-amino-acid polymorphism at Position 435 in IgG3 is sufficient to explain the short half-life of R435-containing IgG3 and demonstrated that H435-IgG3 has a normal half-life of 21 days. Here, we investigated whether the R435 also explains the relatively poor placental transport of IgG3.

STUDY DESIGN AND METHODS:

Sera were collected from paired mothers and newborns at birth. The study included six mothers expressing R435-IgG diagnosed with fetal and neonatal alloimmune thrombocytopenia and treated with intravenous immune globulin (IVIG; containing H435-IgG3, also known as G3m16 or G3m(s,t) allotype), as well as 33 paired samples of both G3m16(-) and G3m16(+) mothers. Placental IgG transport was estimated by comparing cord and maternal concentrations of IgG subclass and G3m16 allotype.

RESULTS:

The placental transport of naturally occurring H435-IgG3 allotypes was significantly more efficient than that of other R435-IgG3 allotypes and was comparable to IgG1 transport.

CONCLUSION:

We demonstrate that the poor maternal-fetal transport of IgG3 is only true for most individuals of western populations where the G3m16 is not common. In G3m16(+) individuals, expressing H435-containing IgG3, IgG3 transport is similar to IgG1, which may give rise to enhanced complications in pregnancy-associated alloimmune disease in ethnic communities where this naturally occurring H435 containing IgG3 allotype is more frequent.

PMID:
23829325
DOI:
10.1111/trf.12334
[Indexed for MEDLINE]
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