Cover Page
The handle
http://hdl.handle.net/1887/136520
holds various files of this Leiden University
dissertation.
Author: Hafkenscheid, L.
Title: Anti Citrullinated Protein Antibodies-IgG variable domain glycosylation in
rheumatoid arthritis
Anti Citrullinated Protein Antibodies-IgG Variable
Domain Glycosylation in Rheumatoid Arthritis
COLOFON
Anti Citrullinated Protein Antibodies-IgG Variable Domain Glycosylation in Rheumatoid Arthritis, Lise Hafkenscheid
ISBN: 978-94-6375-813-0
Anti Citrullinated Protein Antibodies-IgG Variable Domain Glycosylation in Rheumatoid Arthritis
© 2020 Lise Hafkenscheid, 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 manuscript. All published material was reprinted with permission.
The research described in this thesis was performed at the department of rheumatology at the Leiden University Medical Center, The Netherlands.
The research was supported by the Dutch Arthritis Foundation (NR 12-2-403), The Netherlands Organization for Scientific Research (project number 435000033) and the IMI funded project BeTheCure (contract no. 115142-2).
Cover design: Lise Hafkenscheid
Layout and design: Anna Bleeker | persoonlijkproefschrift.nl Printing: Ridderprint | www.ridderprint.nl
Binnenwerk Lise - V1.indd 2
Anti Citrullinated Protein Antibodies-IgG Variable Domain Glycosylation in Rheumatoid Arthritis
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 8 september 2020 klokke 11:15 uur Door
Lise Hafkenscheid Geboren te Amsterdam
Promotor: Prof. Dr. R. E. M. Toes
Co-promotores: Dr. H. U. Scherer
Dr. Y. Rombouts, (Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse,
CNRS, Toulouse, France)
Leden promotiecommissie: Prof. Dr. T. W. J. Huizinga
Prof. Dr. Y. van Kooyk (Department of Molecular Cell Biology and Immunology, VU University medical center, Amsterdam, The Netherlands) Dr. G. Vidarsson (Department of Experimental
Immunohematology, Sanquin Research and
Landsteiner Laboratory, Amsterdam, The
Netherlands)
Binnenwerk Lise - V1.indd 4
TABLE OF CONTENTS
Chapter 1 General introduction 8
Chapter 2 The emerging importance of IgG Fab glycosylation
in immunity 24
Chapter 3 Structural analysis of variable domain glycosylation of
anti-citrullinated protein antibodies in rheumatoid 44
Chapter 4 B-cell receptor sequencing of anti-citrullinated protein antibody (ACPA) IgG-expressing B cells indicates a selective advantage for the introduction of N-glycosylation sites during somatic hypermutation
66
Chapter 5 HappyTools: A software for high-throughput HPLC data
processing and quantitation 74
Chapter 6 N-linked glycans in the variable domain of ACPA-IgG predict
the development of rheumatoid arthritis 94
Chapter 7 The variable domain glycans of ACPA-IgG block the binding pocket for citrullinated antigen without influencing binding strength
112
Chapter 8 Summarizing discussion 134
Appendices Summary 151
Nederlandse samenvatting 157
Curriculum Vitae 163
List of Publications 165
