Cover Page
The handle http://hdl.handle.net/1887/49752 holds various files of this Leiden University dissertation
Author: Plomp, H.R.
Title: Glycoproteomics characterization of immunoglobulins in health and disease
Issue Date: 2017-05-31
Glycoproteomics Characterization of Immunoglobulins in Health and Disease
Henriëtte Rosina Plomp
ISBN: 978-94-6295-651-3
©2017 Henriëtte Rosina Plomp. All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means without permission of the author or the journals holding the copyrights of the published manuscripts. All published material was
reprinted with permission.
The work presented in this thesis was done at the Center for Proteomics and Metabolomics at the Leiden University Medical Center (LUMC), Leiden, The Netherlands.
This work was supported financially by the European Union Seventh Framework Programme HighGlycan project (grant nr. 278535).
Cover design and layout by Henriëtte Rosina Plomp
Glycoproteomics Characterization of Immunoglobulins in Health and Disease
Proefschrift
Ter verkrijging van de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus Prof. Mr. C.J.J.M. Stolker,
volgens besluit van het College voor Promoties te verdedigen op woensdag 31 mei 2017
klokke 15:00 uur
door
Henriëtte Rosina Plomp geboren te Leiderdorp
op 13 november 1987
Promotoren:
Prof. Dr. M. Wuhrer Prof. Dr. A.M. Deelder Co-promotor:
Dr. P. Hensbergen
Leden promotiecommissie:
Prof. Dr. M. de Haas
Dr. G. Vidarsson (Department of Experimental Immunohematology, Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam)
Prof. Dr. C. van Kooten
Dr. R. Dolhain (Department of Rheumatology, Erasmus University Medical Center)
Table of Contents
Chapter 1: Introduction ... 8
1.1: General introduction... 10
1.1.1: Glycan structure ... 10
1.1.2: N-glycosylation ... 11
1.1.3: O-glycosylation ... 12
1.1.4: Functions of glycosylation ... 13
1.1.5: Glycosylation of immunoglobulins ... 14
1.2: Recent advances in Clinical Glycoproteomics of Immunoglobulins (Igs)... 16
1.2.1: Introduction ... 16
1.2.2: IgG ... 19
1.2.3: IgA ... 28
1.2.4: IgM... 30
1.2.5: IgE ... 31
1.2.6: Conclusions and perspectives ... 31
1.3: Scope of Thesis... 33
References ... 34
Chapter 2: Site-specific N-glycosylation analysis of human immunoglobulin E ... 44
2.1: Summary ... 46
2.2: Introduction ... 47
2.3: Methods ... 49
2.4: Results ... 54
2.5: Discussion ... 65
References ... 69
Supplemental information ... 72
Chapter 3: Hinge-region O-glycosylation of human immunoglobulin G3 (IgG3) ... 76
3.1: Summary ... 78
3.2: Introduction ... 79
3.3: Methods ... 81
3.4: Results ... 88
3.5: Discussion ... 98
References ... 102
Supplemental information ... 106
Chapter 4: Galactosylation and sialylation levels of IgG predict relapse in ANCA patients ... 108
4.1: Summary ... 110
4.2: Introduction ... 111
4.3: Methods ... 113
4.4: Results ... 119
4.5: Discussion ... 128
References ... 132
Supplemental information ... 137
Chapter 5: IgG glycosylation is associated with inflammation and metabolic health ... 138
5.1: Summary ... 140
5.2: Introduction ... 141
5.3: Methods ... 143
5.4: Results ... 148
5.5: Discussion ... 153
References ... 157
Supplemental information ... 162
Chapter 6: Discussion ... 164
6.1: General thoughts on glycosylation ... 166
6.2: Analytical challenges ... 166
6.3: Functional aspects of Ig glycosylation ... 169
6.4: IgG glycosylation as a biomarker ... 172
References ... 175
Appendix ... 178
Summary (English) ... 180
Samenvatting (Nederlands) ... 183
List of Abbreviations ... 188
Acknowledgements... 190
Curiculum Vitae ... 191
List of Publications ... 192
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