title: On the perplexingly low rate of transport of IgG2 across the human placenta.
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 κ-, but not λ-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 κ/λ-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 κA and κB. 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.
authors.affiliation: Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Helga K
authors.initials: HK
authors.lastname: Einarsdottir
authors.affiliation: Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Nigel M
authors.initials: NM
authors.lastname: Stapleton
authors.affiliation: Department of Obstetrics and Gynacology, University Medical Centre, Groningen, The Netherlands.
authors.forename: Sicco
authors.initials: S
authors.lastname: Scherjon
authors.affiliation: Centre for Immune Regulation (CIR) and Oslo University Hospital, Department of Immunology, Oslo, Norway.
authors.forename: Jan Terje
authors.initials: JT
authors.lastname: Andersen
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: Rispens
authors.affiliation: Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: C Ellen
authors.initials: CE
authors.lastname: van der Schoot
authors.affiliation: Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Gestur
authors.initials: G
authors.lastname: Vidarsson
mesh_terms: D000361:Agammaglobulinemia / Q000097:blood* / Q000628:therapy; D000818:Animals; D005260:Female; D006207:Half-Life; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D007146:Immunoglobulin lambda-Chains / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D051379:Mice; D010920:Placenta / Q000276:immunology*; D011247:Pregnancy; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport
chemical_list: D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D020033:Protein Isoforms