University of Groningen
T cell-dependent B cell hyperactivity in primary Sjögren's syndrome
Verstappen, Gwenny
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Publication date: 2018
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Verstappen, G. (2018). T cell-dependent B cell hyperactivity in primary Sjögren's syndrome: Biomarker and target for treatment. University of Groningen.
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T cell-dependent B cell hyperactivity
in primary Sjögren’s syndrome
Biomarker and target for treatment
Cover Martijn Wolf | MOTTOW Lay-out Nikki Vermeulen | Ridderprint BV Printing Ridderprint BV | www.ridderprint.nl ISBN (printed version) 978-94-034-0722-7 ISBN (e-book) 978-94-034-0721-0
Printing of this thesis was kindly supported by: the University of Groningen (RuG), the Groningen University Institute for Drug Exploration (GUIDE), the Dutch association of Sjögren’s patients (NVSP), The Binding Site Group, and the Royal Dutch Pharmacists Association (KNMP).
© Gwenny Verstappen
No parts of this publication may be transmitted, in any form or by any means, without permission of the author.
T cell-dependent B cell hyperactivity
in primary Sjögren’s syndrome
Biomarker and target for treatment
PhD thesis
to obtain the degree of PhD at the University of Groningen
on the authority of the Rector Magnificus Prof. E. Sterken
and in accordance with the decision by the College of Deans. This thesis will be defended in public on
Monday 2 July 2018 at 14.30 hours
by
Gwenny Matthea Petronella Johanna Verstappen
born on 16 March 1988 in Nijmegen
Supervisors Prof. H. Bootsma Prof. F.G.M. Kroese Prof. A. Vissink Assessment Committee Prof. T. Dörner Prof. T.W.J. Huizinga Prof. P. Heeringa
TABLE OF CONTENTS
Chapter 1 General introduction 9
Chapter 2 Th17 cells in primary Sjögren’s syndrome: pathogenicity 23 and plasticity
Chapter 3a T follicular regulatory cells from patients with primary Sjögren’s 47
syndrome express decreased levels of CTLA-4
Chapter 3b Is the T Follicular Regulatory / T Follicular Helper Cell Ratio 61
in Blood a Biomarker for Ectopic Lymphoid Structure Formation in Sjögren’s Syndrome?
Chapter 4 Gene expression profiling of epithelium-associated FcRL4+ B cells 67
in primary Sjögren’s syndrome reveals a pathogenic signature
Chapter 5 Serum immunoglobulin free light chains are sensitive biomarkers 89 for monitoring disease activity and treatment response in
primary Sjögren’s syndrome
Chapter 6 B cell depletion therapy normalizes circulating follicular Th cells 111 in primary Sjögren’s syndrome
Chapter 7 The value of rituximab treatment in primary Sjögren’s syndrome 137 Chapter 8 Attenuation of follicular helper T cell–dependent B cell hyperactivity 161
by abatacept treatment in primary Sjögren’s syndrome
Chapter 9 Enhanced Bruton’s tyrosine kinase activity in peripheral blood B 185 lymphocytes from patients with autoimmune disease
Chapter 10 Summary and general discussion 211
Chapter 11 Nederlandse samenvatting 233
Dankwoord 239
Curriculum vitae 245
