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2015 ; 45
(6
): 1085-98
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Evidence that FcRn mediates the transplacental passage of maternal IgE in the
form of IgG anti-IgE/IgE immune complexes
#MMPMID25652137
Bundhoo A
; Paveglio S
; Rafti E
; Dhongade A
; Blumberg RS
; Matson AP
Clin Exp Allergy
2015[Jun]; 45
(6
): 1085-98
PMID25652137
show ga
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.