title: IgG fc N-glycosylation changes in Lambert-Eaton myasthenic syndrome and myasthenia gravis.
abstract: N-glycosylation of the immunoglobulin Fc moiety influences its biological activity by, for example, modulating the interaction with Fc receptors. Changes in IgG glycosylation have been found to be associated with various inflammatory diseases. Here we evaluated for the first time IgG Fc N-glycosylation changes in well-defined antibody-mediated autoimmune diseases, that is, the neurological disorders Lambert-Eaton myasthenic syndrome and myasthenia gravis, with antibodies to muscle nicotinic acetylcholine receptors or muscle-specific kinase. IgGs were purified from serum or plasma by protein A affinity chromatography and digested with trypsin. Glycopeptides were purified and analyzed by MALDI-FTICR-MS. Glycoform distributions of both IgG1 and IgG2 were determined for 229 patients and 56 controls. We observed an overall age and sex dependency of IgG Fc N-glycosylation, which was in accordance with literature. All three disease groups showed lower levels of IgG2 galactosylation compared to controls. In addition, LEMS patients showed lower IgG1 galactosylation. Notably, the galactosylation differences were not paralleled by a difference in IgG sialylation. Moreover, the level of IgG core-fucosylation and bisecting N-acetylglucosamine were evaluated. The control and disease groups revealed similar levels of IgG Fc core-fucosylation. Interestingly, LEMS patients below 50 years showed elevated levels of bisecting N-acetylglucosamine on IgG1 and IgG2, demonstrating for the first time the link of changes in the level of bisecting N-acetylglucosamine with disease.
authors.affiliation: Biomolecular Mass Spectrometry Unit, Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Maurice H J
authors.initials: MH
authors.lastname: Selman
authors.forename: Erik H
authors.initials: EH
authors.lastname: Niks
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Titulaer
authors.forename: Jan J G M
authors.initials: JJ
authors.lastname: Verschuuren
authors.forename: Manfred
authors.initials: M
authors.lastname: Wuhrer
authors.forename: André M
authors.initials: AM
authors.lastname: Deelder
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015331:Cohort Studies; D005260:Female; D005690:Galactose / Q000378:metabolism; D006020:Glycopeptides / Q000737:chemistry* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry* / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry* / Q000378:metabolism; D007249:Inflammation; D015624:Lambert-Eaton Myasthenic Syndrome / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000378:metabolism*; D009369:Neoplasms; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014357:Trypsin / Q000378:metabolism
chemical_list: D006020:Glycopeptides; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D010446:Peptide Fragments; D014357:Trypsin; D005690:Galactose