On the Perplexingly Low Rate of Transport of IgG2 across the Human Placenta

Helga K. Einarsdottir, Nigel M. Stapleton, Sicco Scherjon, Jan Terje Andersen, Theo Rispens, C. Ellen van der Schoot, Gestur Vidarsson*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

22 Citations (Scopus)
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Abstract

The neonatal receptor, FcRn, mediates both serum half-life extension as well as active transport of maternal IgG to the fetus during pregnancy. Therefore, transport efficiency and half-life go hand-in-hand. However, while the half-life of the human IgG2 subclass is comparable to IgG1, the placental transport of IgG2 is not, with the neonatal IgG1 levels generally exceeding maternal levels at birth, but not for IgG2. We hypothesized that the unique short-hinged structure of IgG2, which enables its kappa-, but not lambda-isotype to form at least three different structural isoforms, might be a contributing factor to these differences. To investigate whether there was any preference for either light chain, we measured placental transport of IgG subclasses as well as kappa/lambda-light chain isotypes of IgG1 and IgG2 in 27 matched mother-child pairs. We also studied the half-life of IgG1 and IgG2 light chain isotypes in mice, as well as that of synthesized IgG2 structural isotypes kappa A and kappa B. In order to investigate serum clearance of IgG1 and IgG2 light-chain isotypes in humans, we quantified the relative proportions of IgG1 and IgG2 light chains in hypogammaglobulinemia patients four weeks after IVIg infusion and compared to the original IVIg isotype composition. None of our results indicate any light chain preference in either of the FcRn mediated mechanisms; half-life extension or maternal transport.

Original languageEnglish
Article numbere108319
Number of pages9
JournalPLoS ONE
Volume9
Issue number9
DOIs
Publication statusPublished - 24-Sep-2014

Keywords

  • NEONATAL FC-RECEPTOR
  • IMMUNOGLOBULIN-G
  • HALF-LIFE
  • STRUCTURAL ISOFORMS
  • CRYSTAL-STRUCTURE
  • HUMAN-ANTIBODIES
  • HUMAN-PREGNANCY
  • LIGHT-CHAIN
  • BINDING
  • FETAL

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