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The handle http://hdl.handle.net/1887/28275 holds various files of this Leiden University dissertation.

Author: O’Flynn, Joseph

Title: Properdin-dependent activation and control of immune-homeostasis and autoimmunity

Issue Date: 2014-08-27

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Properdin-dependent activation and control of immune-homeostasis

and autoimmunity

Joseph O’Flynn

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Properdin-dependent activation and control of immune-homeostasis and autoimmunity

© Joseph O’Flynn 2014

All rights are reserved. No parts of this publication may be reproduced, stored, or transmitted in any form or by any means, without permission of the copyright owners.

ISBN: 978-90-5335-890-0 Layout: Joseph O’Flynn Printed by: Ridderprint.nl Published by: Ridderprint.nl

The research presented in this thesis was performed at the Department of Nephrology, Leiden University Medical Center, The Netherlands.

The research described in this thesis was supported by a Marie Curie TranSVIR fellowship (TranSVIR FP7-PEOPLE-ITN-2008 No.238756) funded by the European commission under the 7th framework programme.

Financial support by the Dutch Kidney Foundation, Astellas Pharma B.V, Hycult Biotech and TECO Medical for the publication of this thesis is gratefully acknowledged.

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Properdin-dependent activation and control of immune-homeostasis

and autoimmunity

Proefschrift

ter verkrijging van

de graad van doctor aan de Universiteit Leiden, op gezag van de Rector Magnificus Prof.mr. C.J.J.M. Stolker,

volgens besluit van het College voor Promoties te verdedigen op 28 august 2014

klokke 15.00 uur

door

Joseph O’Flynn (Seosamh O’Floinn)

born in Galway, Republic of Ireland in 1987

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Promotiecommissie

Promotores: Prof. Dr. C. van Kooten

Prof. Dr. M.R. Daha

Overige leden: Prof. Dr. A.J. Rees

Medical University of Vienna, Vienna, Austria Prof. Dr. P.S. Hiemstra

Dr. M.A. Seelen

University Medical Center Groningen, Groningen Dr. L.A. Trouw

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Our greatest glory consists not in never falling, but in rising every time we fall.

Oliver Goldsmith

(10 November 1730 - 4 April 1774)

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Contents

Chapter 1: General Introduction 9 Chapter 2: Nucleosomes and C1q bound to glomerular endothelial cells serve

as targets for autoantibodies and determine complement activation.

Mol Immunol 49 (2011) 75–83. 29

Chapter 3: Properdin binding independent of complement activation in an in-vivo model of anti-GBM disease.

In preparation. 49

Chapter 4: Purification and functional analysis of human properdin.

Methods Mol Biol. 2014;1100:161-7. 65 Chapter 5: Myeloperoxidase directs properdin-mediated complement

activation.

J Innate Immun 2014;6(4):417-25. 75 Chapter 6: CRP as a novel inhibitor of Properdin and complement activation.

In preparation. 91

Chapter 7: Properdin and factor H production by human dendritic cells is differentially regulated by IFNγ and has a functional role in the T cell stimulatory capacity of dendritic cells.

Submitted. 109

Chapter 8: General discussion 131 Chapter 9: Nederlandse samenvatting

Irish and English summary List of abbreviations, Curriculum vitae, Acknowledgements,

Bibliography 147

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