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Cover Page

The handle

http://hdl.handle.net/1887/139216

holds various files of this Leiden

University dissertation.

Author: Lubbers, R.

Title: Complement biology in health and disease

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Complement biology in health and disease

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COLOPHON

Complement biology in health and disease ISBN 978-94-6416-268-4

Layout and design: Birgit Vredenburg | persoonlijkproefschrift.nl Printing: Ridderprint | www.ridderprint.nl

The research described in this thesis was carried out at the department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.

Financial support by the Dutch Arthritis Society for the publication of this thesis is gratefully acknowledged.

Copyright © Rosalie Lubbers

All rights reserved. No part of this thesis may be reproduced, stored or transmitted in any way or by any means without the prior permission of the author, or when applicable, of the publishers of the scientific papers. All published material was reprinted with permission.

RosalieLubbers_BNW.indd 2

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Complement biology in health and disease 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 College voor Promoties te verdedigen op donderdag 21 januari 2021

klokke 16:15 uur door Rosalie Lubbers geboren te Hardenberg

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PROMOTORES

Prof. Dr. R.E.M. Toes Prof. Dr. T.W.J. Huizinga

CO-PROMOTOR

Dr. L.A. Trouw

PROMOTIECOMMISSIE

Prof. Dr. C. van Kooten

Dr. I. Jongerius (Sanquin, Amsterdam) Prof. Dr. S. Rooijakkers (UMC Utrecht) Dr. F.J. Beurskens (Genmab, Utrecht)

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TABLE OF CONTENTS

Chapter 1 General introduction 9

Chapter 2 Complement component C1q is locally produced by isolated articular

chondrocytes 25

Chapter 3 Complement C3 cleavage by Cathepsin-L leads to formation of

C3a-desArg and is not essential for survival in a HAP-1 model cell line 45

Chapter 4 Complement component C1q as serum biomarker to detect active

tuberculosis 69

Chapter 5 Analysis of the endogenous complement regulator C1-inhibitor, the

product of SERPING1, in active tuberculosis 93

Chapter 6 Systemic and pulmonary C1q as biomarker of progressive disease in

experimental non-human primate tuberculosis 113

Chapter 7 Complex medical history of a lupus patient with a compound

heterozygous mutation in C1QC 139

Chapter 8 Carbamylation reduces capacity of IgG for hexamerisation and

complement activation 151

Chapter 9 Summary and general discussion 173

Addendum Nederlandse samenvatting 190

Curriculum Vitae 197

List of publications 198

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