Leiden University Scholarly Publications

Persistent URL of this record https://hdl.handle.net/1887/118022

In Collections

This item can be found in the following collections:

Selman, M.H.J.; Niks, E.H.; Titulaer, M.J.; Verschuuren, J.J.G.M.; Wuhrer, M.; Deelder, A.M. (2011)

IgG Fc N-Glycosylation Changes in Lambed-Eaton Myasthenic Syndrome and Myasthenia Gravis

Article / Letter to editor
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...Show moreN-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.Show less
antibody glycopeptides myasthenia gravis glycosylation mass spectrometry post-translational modification LEMS rheumatoid-arthritis immunoglobulin-g human-serum antiinflammatory activity structural-changes heavy-chains gamma-riii follow-up antibodies galactosylation
All authors
Selman, M.H.J.; Niks, E.H.; Titulaer, M.J.; Verschuuren, J.J.G.M.; Wuhrer, M.; Deelder, A.M.
Date
2011-01-31
Journal
Journal of Proteome Research
Volume
10
Issue
1
Pages
143 - 152
DOI
doi:10.1021/pr1004373