title: Comparison of Fc N-Glycosylation of Pharmaceutical Products of Intravenous Immunoglobulin G.
abstract: Intravenous immunoglobulin (IVIg) products from different pharmaceutical companies vary in composition, in part because of the selected blood donors and production process. N-glycosylation of the Fc-portion of IgG varies between blood donors and may influence both the side-effects and therapeutic effectiveness of IVIg. At present, the variation in Fc N-glycosylation between IVIg products has not been defined. Utilizing mass spectrometry, we performed relative quantitation of the Fc N-glycosylation of IgG, assessing a total of 154 unique lot numbers of IVIg. Seven products showed comparable Fc N-glycosylation, with only one product differing from the others in all glycosylation features (galactosylation, sialylation, fucosylation and bisecting N-acetylglucosamine). However, the mean difference did not exceed 3%. Within product variation was present to a minor degree, but largely indistinguishable from analytical variation. In conclusion, we expect that the minor variation in Fc N-glycosylation between IVIg products has a small effect, if any, on the biological activity.
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Willem Jan R
authors.initials: WJ
authors.lastname: Fokkink
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: David
authors.initials: D
authors.lastname: Falck
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Tom C M
authors.initials: TC
authors.lastname: Santbergen
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Ruth
authors.initials: R
authors.lastname: Huizinga
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands; Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, Division of BioAnalytical Chemistry, VU University, Amsterdam, The Netherlands.
authors.forename: Manfred
authors.initials: M
authors.lastname: Wuhrer
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Bart C
authors.initials: BC
authors.lastname: Jacobs
mesh_terms: D005260:Female; D006031:Glycosylation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry*; D007074:Immunoglobulin G / Q000737:chemistry*; D016756:Immunoglobulins, Intravenous / Q000737:chemistry*; D008297:Male
chemical_list: D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous