title: Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn.
abstract: Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. HDFN is most often caused by anti-D but may also occur due to anti-K, -c- or -E. We recently found N-linked glycosylation of anti-D to be skewed towards low fucosylation, thereby increasing the affinity to IgG-Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. Anti-c, -E and -K show - independent of the event that had led to immunisation - a different kind of Fc-glycosylation compared to that of the total IgG fraction, but with less pronounced differences compared to anti-D. High Fc-galactosylation and sialylation of anti-c correlated with HDFN disease severity, while low anti-K Fc-fucosylation correlated with severe fetal anaemia. IgG-Fc glycosylation of anti-RBC antibodies is shaped depending on the antigen. These features influence their clinical potency and may therefore be used to predict severity and identify those needing treatment.
authors.affiliation: Department of Experimental Immunohaematology, Sanquin Research, Amsterdam, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Myrthe E
authors.initials: ME
authors.lastname: Sonneveld
authors.affiliation: Department of Immunohaematotology Diagnostics, Sanquin, Amsterdam, the Netherlands.
authors.forename: Joke
authors.initials: J
authors.lastname: Koelewijn
authors.affiliation: Department of Immunohaematotology Diagnostics, Sanquin, Amsterdam, the Netherlands.|Centre for Clinical Transfusion Research, Sanquin Research and Dept of Immunohaematology and Blood Transfusion of Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: Masja
authors.initials: M
authors.lastname: de Haas
authors.affiliation: Department of Experimental Immunohaematology, Sanquin Research, Amsterdam, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Jon
authors.initials: J
authors.lastname: Admiraal
authors.affiliation: Centre for Proteomics and Metabolomics, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: Rosina
authors.initials: R
authors.lastname: Plomp
authors.affiliation: Centre for Proteomics and Metabolomics, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: Carolien A M
authors.initials: CA
authors.lastname: Koeleman
authors.affiliation: Centre for Proteomics and Metabolomics, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: Agnes L
authors.initials: AL
authors.lastname: Hipgrave Ederveen
authors.affiliation: Department of Immunohaematotology Diagnostics, Sanquin, Amsterdam, the Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Ligthart
authors.affiliation: Centre for Proteomics and Metabolomics, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: Manfred
authors.initials: M
authors.lastname: Wuhrer
authors.affiliation: Department of Experimental Immunohaematology, Sanquin Research, Amsterdam, 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 Immunohaematology, Sanquin Research, Amsterdam, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Gestur
authors.initials: G
authors.lastname: Vidarsson
mesh_terms: D000328:Adult; D001789:Blood Group Antigens / Q000276:immunology; D004899:Erythroblastosis, Fetal / Q000175:diagnosis / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006031:Glycosylation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism*; D007231:Infant, Newborn; D007518:Isoantibodies / Q000097:blood*; D008297:Male; D011247:Pregnancy; D012720:Severity of Illness Index
chemical_list: D001789:Blood Group Antigens; D007141:Immunoglobulin Fc Fragments; D007518:Isoantibodies
keywords: Antibodies; Fc-glycosylation; Haemolytic anaemia; Immunology; Red cell antigens