Comparison of the Fc glycosylation of fetal and maternal immunoglobulin G.

Helga K Einarsdottir,Gestur Vidarsson,André M Deelder,Rick Kapur,Carolien A M Koeleman,Sicco Scherjon,Manfred Wuhrer,Maurice H J Selman,C Ellen Van Der Schoot

doi:10.1007/s10719-012-9381-6

Helga K Einarsdottir, Gestur Vidarsson + Show 7 more

Open Access

https://doi.org/10.1007/s10719-012-9381-6

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Abstract

Human immunoglobulin G (IgG) molecules are composed of two Fab portions and one Fc portion. The glycans attached to the Fc portions of IgG are known to modulate its biological activity as they influence interaction with both complement and various cellular Fc receptors. IgG glycosylation changes significantly with pregnancy, showing a vast increase in galactosylation and sialylation and a concomitant decrease in the incidence of bisecting GlcNAc. Maternal IgGs are actively transported to the fetus by the neonatal Fc receptor (FcRn) expressed in syncytiotrophoblasts in the placenta, providing the fetus and newborn with immunological protection. Two earlier reports described significant differences in total glycosylation between fetal and maternal IgG, suggesting a possible glycosylation-selective transport via the placenta. These results might suggest an alternative maternal transport pathway, since FcRn binding to IgG does not depend on Fc-glycosylation. These early studies were performed by releasing N-glycans from total IgG. Here, we chose for an alternative approach analyzing IgG Fc glycosylation at the glycopeptide level in an Fc-specific manner, providing glycosylation profiles for IgG1 and IgG4 as well as combined Fc glycosylation profiles of IgG2 and 3. The analysis of ten pairs of fetal and maternal IgG samples revealed largely comparable Fc glycosylation for all the analyzed subclasses. Average levels of galactosylation, sialylation, bisecting GlcNAc and fucosylation were very similar for the fetal and maternal IgGs. Our data suggest that the placental IgG transport is not Fc glycosylation selective.

Highlights

Human immunoglobulin G (IgG) molecules are composed of two fragment antigen binding (Fab) portions and one fragment crystallizable (Fc) portion
IgGs occur in different subclasses (IgG1, IgG2, IgG3, and IgG4), named in order of decreasing abundance [1]. They are formed from two heavy chains and two lights chains which together form two fragment antigen binding (Fab) portions and one fragment crystallizable (Fc) portion, which is distinct between the subclasses, and influences their specific
IgG was subjected to tryptic cleavage, and resulting IgG Fc glycopeptides were analyzed using a recently established nano-LC-MS method employing a sheath-flow ESI sprayer

Summary

Introduction

Human immunoglobulin G (IgG) molecules are composed of two Fab portions and one Fc portion. IgG glycosylation changes significantly with pregnancy, showing a vast increase in galactosylation and sialylation and a concomitant decrease in the incidence of bisecting GlcNAc. Maternal IgGs are actively transported to the fetus by the neonatal Fc receptor (FcRn) expressed in syncytiotrophoblasts in the placenta, providing the fetus and newborn with immunological protection. Two earlier reports described significant differences in total glycosylation between fetal and maternal IgG, suggesting a possible glycosylationselective transport via the placenta. These results might suggest an alternative maternal transport pathway, since FcRn binding to IgG does not depend on Fc-glycosylation. These early studies were performed by releasing N-glycans from total IgG. The reduced fucosylation of IgG1 may be important in pathological situations, e.g. during pregnancies complicated with the formation of maternal IgG against fetal platelets, which we found to be highly skewed towards the afucosylated kind [17]

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