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Evidence that F c R n mediates the transplacental passage of maternal IgE in the form of I g G anti‐ I g E / I g E immune complexes
Author(s) -
Bundhoo A.,
Paveglio S.,
Rafti E.,
Dhongade A.,
Blumberg R. S.,
Matson A. P.
Publication year - 2015
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12508
Subject(s) - immunoglobulin e , immunology , antibody , biology , chemistry
Summary 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 ( IC s) 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 IC s 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 IC s. Results Maternal and CB serum concentrations of IgG anti‐IgE/IgE IC s were highly correlated, regardless of maternal allergic status. IgG anti‐IgE/IgE IC s 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 IC s, 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 IC s. 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 IC s. These findings challenge the widespread perception that maternal IgE does not cross the placenta. Measuring maternal or CB levels of IgG anti‐IgE/IgE IC s may be a more accurate predictor of allergic risk.