title: Evidence that FcRn mediates the transplacental passage of maternal IgE in the form of IgG anti-IgE/IgE immune complexes.
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
  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.
authors: Division of Neonatology, Connecticut Children's Medical Center, Hartford, CT, USA.|Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, USA.
authors: A
authors: A
authors: Bundhoo
authors: Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, USA.
authors: S
authors: S
authors: Paveglio
authors: Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, USA.
authors: E
authors: E
authors: Rafti
authors: Division of Neonatology, Connecticut Children's Medical Center, Hartford, CT, USA.|Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, USA.
authors: A
authors: A
authors: Dhongade
authors: Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA, USA.
authors: R S
authors: RS
authors: Blumberg
authors: Division of Neonatology, Connecticut Children's Medical Center, Hartford, CT, USA.|Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, USA.|Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, USA.
authors: A P
authors: AP
authors: Matson
mesh_terms: D000328:Adult; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies; D002460:Cell Line; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D010920:Placenta / Q000276:immunology* / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding; D021381:Protein Transport; D011961:Receptors, Fc / Q000378:metabolism*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; C100688:Fc receptor, neonatal
keywords: FcRn; IgG anti-IgE; allergy; autoantibodies; cord blood; immune complexes; infant; mother; placenta
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