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HFcRn-mediated transplacental immunoglobulin G transport: Protection of and threat to the human fetus and newborn

HFcRn-mediierter transplazentarer Immunglobulin G-Transport: Schutz und Gefahr für den menschlichen Föten und das Neugeborene

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Summary

Die Bildung eigener Immunglobuline setzt beim Menschen erst nach der Geburt ein. Um Infektionen während der fötalen Periode sowie in den ersten Monaten nach der Geburt zu minimieren, wird der Fötus während der Schwangerschaft mit mütterlichen Immunglobulin G (IgG)-Antikörpern passiv immunisiert. Dieser Artikel beschreibt den Mechanismus des transplazentaren IgG-Transports durch Synzytiotrophoblast und Endothelzellen der fötalen Kapillaren, der durch den MHC Klasse I-ähnlichen, neonatalen Fc-Rezeptor, hFcRn vermittelt wird. Wichtige Eigenschaften des IgG-Transports, wie Unterschiede im Transport der IgG-Subklassen oder der eingeschränkte IgG-Transport vor dem dritten Trimenon, wodurch es bei frühgeborenen Kindern (<35 Wochen) zur Abwehrschwäche kommen kann, werden erläutert. Da hFcRn zwischen schützenden und potentiell gefährlichen IgG-Antikörpern nicht unterscheiden kann, erreichen den Föten auch maternale auto- und alloimmun sowie therapeutische Antikörper. Die Folgen dieses Transportes, der zu schweren Erkrankungen der Neugeborenen führen kann, werden zusammengefasst.

Summary

In human newborns, endogenous levels of plasma immunoglobulin G (IgG) begin to rise slowly after birth following exposure to the environment. For immunoprotection during fetal and early neonatal life, maternal IgG is provided by transplacental transport. While cellular immunoprotective IgG effects are mainly triggered by FcγRI, -RII and -RIII, transplacental IgG transfer is mediated by the MHC class I-like neonatal Fc-receptor, hFcRn. This compact review explains the mechanism of hFcRn-mediated IgG transcytosis across the placental barrier – syncytiotrophoblast and fetal endothelial cells. Restrictions of this IgG transport are summarized. These include IgG subclass discrimination and limited IgG transport before the third trimester that can cause insufficient protection from infections of preterm (≤35th week) delivered babies. As hFcRn does not discriminate beneficial from hazardous IgGs, maternal auto- and alloimmune as well as therapeutic antibodies can reach the fetus. The consequences including severe diseases of the newborn are summarized in this article.

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Authors and Affiliations

  1. Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria

    Isabella Ellinger & Renate Fuchs

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  1. Isabella Ellinger
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  2. Renate Fuchs
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Correspondence to Isabella Ellinger.

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Ellinger, I., Fuchs, R. HFcRn-mediated transplacental immunoglobulin G transport: Protection of and threat to the human fetus and newborn. Wien Med Wochenschr 162, 207–213 (2012). https://doi.org/10.1007/s10354-012-0085-0

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  • DOI: https://doi.org/10.1007/s10354-012-0085-0

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