1. A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy
- Author
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Dave Jackson, C. Ellen van der Schoot, Theo Rispens, Iwan Kustiawan, Masja de Haas, Mette Kjaer Killie, Dennis Blank, Helga K. Einarsdottir, Terje E. Michaelsen, Belinda Kumpel, Carolien A. M. Koeleman, Leendert Porcelijn, Bjørn Skogen, Anne Vestrheim, Remco Visser, André M. Deelder, Rick Kapur, Manfred Wuhrer, Gestur Vidarsson, Univ Amsterdam, Acad Med Ctr, Dept Expt Immunohematol, NL-1105 AZ Amsterdam, Netherlands, Univ Amsterdam, Acad Med Ctr, Dept Immunopathol, Sanquin Res & Landsteiner Lab, NL-1105 AZ Amsterdam, Netherlands, Norwegian Inst Publ Hlth, Dept Bacteriol & Immunol, Oslo, Norway, Univ Oslo, Sch Pharm, Oslo, Norway, Leiden Univ, Med Ctr, Biomol Mass Spectrometry Unit, Leiden, Netherlands, Sanquin, Thrombocyte & Leukocyte Serol, Amsterdam, Netherlands, Natl Hlth Serv Blood & Transplant, Bristol Inst Transfus Sci, Bristol, Avon, England, Univ Tromso, Inst Med Biol, Tromso, Norway, Univ Hosp North Norway, Tromso, Norway, Other departments, Landsteiner Laboratory, and Clinical Haematology
- Subjects
Blood Platelets ,medicine.medical_specialty ,Glycosylation ,Immunology ,Biochemistry ,Immunoglobulin G ,Mass Spectrometry ,Monocytes ,Isoantibodies ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,HLA Antigens ,Pregnancy ,Internal medicine ,Medicine ,Humans ,Fucosylation ,030304 developmental biology ,Fucose ,0303 health sciences ,Fetus ,biology ,business.industry ,Platelet Count ,Postpartum Period ,Antibody titer ,Antibodies, Monoclonal ,Cell Biology ,Hematology ,Surface Plasmon Resonance ,medicine.disease ,Isotype ,Recombinant Proteins ,3. Good health ,Immunoglobulin Fc Fragments ,Thrombocytopenia, Neonatal Alloimmune ,Endocrinology ,Glucose ,Neonatal alloimmune thrombocytopenia ,biology.protein ,Female ,Antibody ,Asparagine ,business ,030215 immunology - Abstract
To 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. 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, 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. Sanquin/PPOC-09- 025 Landsteiner Foundation for Blood Transfusion/0721 info:eu-repo/grantAgreement/EC/FP7/278535
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- 2014
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