A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Koeleman, Carolien A M
Einarsdottir, Helga K
Deelder, André M
Killie, Mette Kjaer
Michaelsen, Terje E
de Haas, Masja
van der Schoot, C Ellen
MetadataShow full item record
CitationBlood 2014, 123 (4):471-80
AbstractImmunoglobulin 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, compared with antibodies with a high amount of Fc fucose. Consequently, these antibodies with a low amount of Fc fucose showed enhanced phagocytosis of platelets using FcγRIIIb(+) polymorphonuclear cells or FcγRIIIa(+) monocytes as effector cells, but not with FcγRIIIa(-) monocytes. In addition, the degree of anti-HPA-1a fucosylation correlated positively with the neonatal platelet counts in FNAIT, and negatively to the clinical disease severity. In contrast to the FNAIT patients, no changes in core fucosylation were observed for anti-HLA antibodies in refractory thrombocytopenia (post platelet transfusion), indicating that the level of fucosylation may be antigen dependent and/or related to the immune milieu defined by pregnancy.
DescriptionTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.
- Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia.
- Authors: Sonneveld ME, Natunen S, Sainio S, Koeleman CA, Holst S, Dekkers G, Koelewijn J, Partanen J, van der Schoot CE, Wuhrer M, Vidarsson G
- Issue date: 2016 Jul
- Core fucosylation and IgG function in NAIT.
- Authors: Aster RH
- Issue date: 2014 Jan 23
- Inhibition of HPA-1a alloantibody-mediated platelet destruction by a deglycosylated anti-HPA-1a monoclonal antibody in mice: toward targeted treatment of fetal-alloimmune thrombocytopenia.
- Authors: Bakchoul T, Greinacher A, Sachs UJ, Krautwurst A, Renz H, Harb H, Bein G, Newman PJ, Santoso S
- Issue date: 2013 Jul 18
- Regulated glycosylation patterns of IgG during alloimmune responses against human platelet antigens.
- Authors: Wuhrer M, Porcelijn L, Kapur R, Koeleman CA, Deelder A, de Haas M, Vidarsson G
- Issue date: 2009 Feb
- Predicting risk severity and response of fetal neonatal alloimmune thrombocytopenia.
- Authors: Salomon O, Rosenberg N
- Issue date: 2013 Aug