NDLI: Evidence that FcRn mediates the transplacental passage of maternal IgE in the form of IgG anti-IgE/IgE immune complexes.

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Evidence that FcRn mediates the transplacental passage of maternal IgE in the form of IgG anti-IgE/IgE immune complexes.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bundhoo, A. Paveglio, S. Rafti, E. Dhongade, A. Blumberg, R. S. Matson, A. P.
Description	Country affiliation: United States Author Affiliation: Bundhoo A ( Division of Neonatology, Connecticut Children's Medical Center, Hartford, CT, USA.); Paveglio S ( Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, USA.); Rafti E ( Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, USA.); Dhongade A ( Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, USA.); Blumberg RS ( Division of Neonatology, Connecticut Children's Medical Center, Hartford, CT, USA.); Matson AP ( Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, USA.)
Abstract	BACKGROUND: The mechanism(s) responsible for acquisition of maternal antibody isotypes other than IgG are not fully understood. This uncertainty is a major reason underlying the continued controversy regarding whether cord blood (CB) IgE originates in the mother or fetus. OBJECTIVE: To investigate the capacity of maternal IgE to be transported across the placenta in the form of IgG anti-IgE/IgE immune complexes (ICs) and to determine the role of the neonatal Fc receptor (FcRn) in mediating this process. METHODS: Maternal and CB serum concentrations of IgE, IgG anti-IgE, and IgG anti-IgE/IgE ICs were determined in a cohort of allergic and non-allergic mother/infant dyads. Madin-Darby canine kidney (MDCK) cells stably transfected with human FcRn were used to study the binding and transcytosis of IgE in the form of IgG anti-IgE/IgE ICs. RESULTS: Maternal and CB serum concentrations of IgG anti-IgE/IgE ICs were highly correlated, regardless of maternal allergic status. IgG anti-IgE/IgE ICs generated in vitro bound strongly to FcRn-expressing MDCK cells and were transcytosed in an FcRn-dependent manner. Conversely, monomeric IgE did not bind to FcRn and was not transcytosed. IgE was detected in solutions of transcytosed IgG anti-IgE/IgE ICs, even though essentially all the IgE remained in complex form. Similarly, the majority of IgE in CB sera was found to be complexed to IgG. CONCLUSIONS AND CLINICAL RELEVANCE: These data indicate that human FcRn facilitates the transepithelial transport of IgE in the form of IgG anti-IgE/IgE ICs. They also strongly suggest that the majority of IgE in CB sera is the result of FcRn-mediated transcytosis of maternal-derived IgG anti-IgE/IgE ICs. These findings challenge the widespread perception that maternal IgE does not cross the placenta. Measuring maternal or CB levels of IgG anti-IgE/IgE ICs may be a more accurate predictor of allergic risk.
File Format	HTM / HTML
ISSN	09547894
e-ISSN	13652222
DOI	10.1111/cea.12508
Journal	Clinical & Experimental Allergy
Issue Number	6
Volume Number	45
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2015-06-01
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Discipline Immunology Antibodies, Anti-idiotypic Immunology Antigen-antibody Complex Histocompatibility Antigens Class I Metabolism Immunoglobulin E Immunoglobulin G Placenta Receptors, Fc Animals Autoantibodies Cell Line Fetal Blood Hypersensitivity Blood Pregnancy Protein Binding Protein Transport Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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