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The handle http://hdl.handle.net/1887/18690 holds various files of this Leiden University dissertation.

Author: Selman, Maurice Henricus Johannes

Title: Glycosylation analysis of immunoglobulin G : method development and clinical applications

Issue Date: 2012-04-17

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Glycosylation analysis of immunoglobulin G:

method development and clinical applications

Maurice Henricus Johannes Selman

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published material was reprinted with permission.

The work presented in this thesis was performed at the Biomolecular Mass Spectrometry Unit, Department of Parasitology from the Leiden University Medical Center.

The studies described in this thesis were financially supported by Hoffmann la Roche.

The printing of this thesis was financially supported by Hoffmann la Roche

Cover design: Dirk-Jan de Graaf

Layout and printing: Off Page, www.offpage.nl

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Glycosylation analysis of immunoglobulin G:

method development and clinical applications

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden,

op gezag van de Rector Magnificus Prof.mr. P.F. van der Heijden, volgens besluit van het College voor Promoties

te verdedigen op dinsdag 17 april 2012 klokke 16:15 uur

door

Maurice Henricus Johannes Selman

geboren te Heteren op 12 april 1980

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Dr. M. Wuhrer Overige leden:

Prof. Dr. M. Yazdanbakhsh Prof. Dr. P.E. Slagboom Prof. Dr. H.S. Overkleeft

Prof. Dr. G.J. de Jong (Utrecht University, Departement of Biomedical Analysis) Prof. Dr. R. Geyer (Institute of Biochemistry, Justus-Liebig-University Giessen, Germany) Dr. N. Engler (F. Hoffmann - La Roche Ltd, Basel, Switzerland)

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Table of contents

Chapter 1 IgG glycosylation analysis 7

Method development

Chapter 2 Fc specific IgG glycosylation profiling by robust nano-reversed 25 phase HPLC-MS using a sheath-flow ESI sprayer interface

Chapter 3 Cotton HILIC SPE microtips for micro-scale purification and 45 enrichment of glycans and glycopeptides

Chapter 4 Immunoglobulin G glycopeptide profiling by matrix-assisted laser 65 desorption ionization Fourier transform ion cyclotron resonance mass spectrometry

Chapter 5 MALDI-TOF-MS analysis of sialylated glycans and glycopeptides 87 using 4-chloro-α-cyanocinnamic acid matrix

Applications

Chapter 6 Changes in antigen-specific IgG1 Fc N-glycosylation upon 115 influenza and tetanus vaccination

Chapter 7 IgG Fc N-glycosylation changes in Lambert-Eaton myasthenic 135 syndrome and myasthenia gravis

Chapter 8 General discussion 155

Addendum Reference list 165

Summary 172

Samenvatting 175

Abbreviations 178

Acknowledgements 180

Curriculum Vitae 182

List of publications 183

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