Mechanisms of disease and therapy in severe Juvenile Idiopathic Arthritis PDF
Preview Mechanisms of disease and therapy in severe Juvenile Idiopathic Arthritis
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 Chapter 1 R1 R2 1 R3 R4 R5 R6 R7 R8 R9 R10 R11 R12 R13 R14 R15 R16 R17 R18 R19 R20 R21 R22 R23 R24 R25 R26 R27 R28 R29 R30 R31 R32 R33 R34 R35 R36 R37 R38 R39 10
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