Mechanisms of disease and therapy in severe Juvenile Idiopathic Arthritis

242 Pages·2013·6.19 MB·English

Mechanisms of disease and therapy
in severe Juvenile Idiopathic Arthritis
Bas Vastert
ISBN: 978-94-6108-438-5
© SJ Vastert, EJM Wehrens, W de Jager, NM Wulffraat and B.J. Prakken, 2013
The copyright of articles that have been published or accepted for publication has been transferred to the
respective journals.
All rights reserved. No part of this thesis may be reproduced, stored in a retrieval system, or transmitted in any
form or by any means without prior written permission of the author.
Cover: Boris en Bloeme.
Layout and printing: Gildeprint Drukkerijen, Enschede.
Printing of this thesis has been supported by:
Het Reumafonds, de Jurriaanse Stichting, Infection & Immunity Center Utrecht, TEVA Pharma NL, Pfizer,
Roche Nederland BV, Swedish Orphan Biovitrum AB, Stockholm, Sweden.
Address for correspondence:
SJ Vastert, Wilhelmina Children´s Hospital, department of pediatric rheumatology and immunology,
KC030630, PO Box 85090, 3508 AB, Utrecht, the Netherlands.
e-mail: [email protected]
Mechanisms of disease and therapy
in severe Juvenile Idiopathic Arthritis
Inzicht in mechanismen van ziekte en therapie in ernstige
Juveniele Idiopathische Artritis
(met een samenvatting in het Nederlands)
Proefschrift
ter verkrijging van de graad van doctor
aan de Universiteit Utrecht
op gezag van de rector magnificus prof.dr. G.J. van der Zwaan
ingevolge het besluit van het college voor promoties
in het openbaar te verdedigen
op donderdag 30 mei 2013 des middags te 2.30 uur
door
Sebastiaan Jozef Vastert
geboren op 15 mei 1975 te Delft
Promotoren: Prof. dr. A.B.J. Prakken
Prof. dr. N.M. Wulffraat
Prof. dr. W. Kuis
Co-promotor: dr. W. de Jager
Dit proefschrift werd (mede) mogelijk gemaakt met financiële steun van het Reumafonds en
een NWO VIDI beurs toegekend aan prof. dr. A.B.J. Prakken.
voor mijn ouders

Contents
Chapter 1 General introduction 9
Chapter 2 Systemic JIA: New developments in the understanding of the 29
pathophysiology and therapy
Best Pract Res Clin Rheumatol. 2009
Chapter 3 Mutations in the perforin gene can be linked to macrophage 45
activation syndrome in patients with systemic onset juvenile
idiopathic arthritis
Rheumatology 2010
Chapter 4 Defective phosphorylation of Interleukin-18 Receptor β causes 63
impaired Natural Killer cell function in systemic-onset Juvenile
Idiopathic Arthritis
Arthritis and Rheumatism 2009
Chapter 5 IL-1RA restores the IL-18-NK cell axis in systemic Juvenile Idiopathic 83
Arthritis
submitted
Chapter 6 Effectiveness of first line use of recombinant IL-1RA treatment in 107
steroid naïve systemic juvenile idiopathic arthritis: results of a
prospective cohort study
submitted
Chapter 7 FOXP3+CD4+Tregs lose suppressive potential but remain 125
anergic during transient inflammation in human
European Journal of Immunology 2011
Chapter 8 Methotrexate treatment enhances T cell responsiveness in 151
Juvenile Idiopathic Arthritis
Chapter 9 Anti-TNFα therapy targets PKB/c-akt induced resistance of effector 167
cells to suppression in Juvenile Idiopathic Arthritis
submitted
Chapter 10 Autologous stem cell transplantation for autoimmunity induces 181
immunologic self-tolerance by reprogramming autoreactive T cells
and restoring the CD4+CD25+ immune regulatory network
Blood 2006
Chapter 11 Summary and general discussion 203
Nederlandse samenvatting 233
Dank 237
Curriculum Vitae 243
List of publications 245
GenerAl IntroduCtIon
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