A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy.

R. Kapur, I. Kustiawan, A. Vestrheim, C.A. Koeleman, R. Visser, H.K. Einarsdottir, L. Porcelijn, D. Jackson, B. Kumpel, A.M. Deelder, D. Blank, B. Skogen, M.K. Killie, T.E. Michaelsen, M. de Haas, T. Rispens, C.E. van der Schoot, M. Wuhrer, G. Vidarsson

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Immunoglobulin G (IgG) formed during pregnancy against human platelet antigens (HPAs) of the fetus mediates fetal or neonatal alloimmune thrombocytopenia (FNAIT). Because antibody titer or isotype does not strictly correlate with disease severity, we investigated by mass spectrometry variations in the glycosylation at Asn297 in the IgG Fc because the composition of this glycan can be highly variable, affecting binding to phagocyte IgG-Fc receptors (FcγR). We found markedly decreased levels of core fucosylation of anti-HPA-1a-specific IgG1 from FNAIT patients (n = 48), but not in total serum IgG1. Antibodies with a low amount of fucose displayed higher binding affinity to FcγRIIIa and FcγRIIIb, but not to FcγRIIa, comparedwith antibodieswith a high amount of Fc fucose. Consequently, these antibodies with a low amount of Fc fucose showed enhanced phagocytosis of platelets using FcγRIIIb
Original languageEnglish
Pages (from-to)471-480
JournalBlood
Volume123
Issue number4
DOIs
Publication statusPublished - 2014
Externally publishedYes

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