paraneoplastic neurological syndromes with anti-hu antibodies

167 Pages·2015·2.26 MB·English

PARANEOPLASTIC NEUROLOGICAL SYNDROMES
WITH ANTI-HU ANTIBODIES
Pathogenesis and treatment
Arjen de Jongste
The studies described in this thesis were performed at the departments of Neurol-
ogy and Medical Oncology of the Erasmus University Medical Center (Rotterdam, The
Netherlands) and the Inserm, U986, Diabetes & Autoimmunity Research Laboratory
(Paris, France).
Part of the research described in this thesis was supported by The Gratama Founda-
tion (Harlingen, The Netherlands), and JDRF, the European Foundation for the Study
of Diabetes, the Fondation Recherche Médicale and the Ile-de-France CODDIM to dr.
R. Mallone.
Printing of this thesis was sponsored by U-Cytech, BD Biosciences and Beckman Coul-
ter.
ISBN: 978-94-6169-589-5
Layout and printing: Optima Grafische Communicatie, Rotterdam, The Netherlands.
Cover design: Optima Grafische Communicatie, Rotterdam, The Netherlands
Copyright: A.H.C. de Jongste, 2014
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, electronic, mechanical, photo-
copying, recording or otherwise without the prior written permission of the copyright
owner.
PARANEOPLASTIC NEUROLOGICAL SYNDROMES
WITH ANTI-HU ANTIBODIES
Pathogenesis and treatment
PARANEOPLASTISCHE NEUROLOGISCHE SYNDROMEN
MET ANTI-HU ANTISTOFFEN
Pathogenese en behandeling
Proefschrift
ter verkrijging van de graad van doctor aan de
Erasmus Universiteit Rotterdam
op gezag van de
rector magnificus
Prof.dr. H.A.P. Pols
en volgens besluit van het College voor Promoties.
De openbare verdediging zal plaatsvinden op
woensdag 28 januari 2015 om 15.30 uur
door
Adriaan Hendrik Cornelis de Jongste
geboren te Rotterdam
PROMOTIECOMMISSIE
Promotor:
Prof.dr. P.A.E. Sillevis Smitt
Overige leden:
Prof.dr. J.J.G.M. Verschuuren
Prof.dr. T. van Gelder
Prof.dr. H. Hooijkaas
Copromotor:
Dr. J.W. Gratama
TABLE OF CONTENTS
Chapter 1 General introduction 9
Part I: Functional T cell analyses
Chapter 2 Three sensitive assays do not provide evidence for 19
circulating HuD-specific T cells in the blood of patients
with paraneoplastic neurological syndromes with anti-Hu
antibodies
Neuro-Oncology. July 2012;14(7):841-848
Part II: Cellular composition of cerebrospinal fluid
Chapter 3 Flow cytometric characterization of cerebrospinal fluid cells 35
Cytometry Part B: Clinical Cytometry. May 12 2011(80B):271-281
Chapter 4 Effector memory and late memory T cells accumulate in 61
the blood of CMV-carrying individuals but not in their
cerebrospinal fluid
Cytometry Part B: Clinical Cytometry. Jul-Aug 2013;84(4):218-221
Chapter 5 Elevated numbers of regulatory T cells, central memory T cells 69
and class-switched B cells in cerebrospinal fluid of patients
with anti-Hu antibody associated paraneoplastic neurological
syndromes
Journal of Neuroimmunology. 2013; 258 (1-2): 85–90
Chapter 6 Use of TransFix™ cerebrospinal fluid storage tubes prevents 87
cellular loss and enhances flow cytometric detection of
malignant hematological cells after 18 hours of storage
Cytometry Part B: Clinical Cytometry. Jul 2014;86(4):272-279
Part III: Clinical studies
Chapter 7 Current and future approaches for treatment of paraneoplastic 105
neurological syndromes with well characterized onconeural
antibodies
Expert Opinion on Orphan Drugs. 2014;5(2): 483-495
Chapter 8 A prospective open-label study of sirolimus for the treatment 135
of anti-Hu associated paraneoplastic neurological syndromes
Neuro-Oncology. Epub ahead of print, doi:10.1093/neuonc/
nou126
Chapter 9 Summary and discussion 147
Appendices 155
Samenvatting 157
Dankwoord 159
PhD portfolio 163
Curriculum vitae 165
List of publications 167

1
General introduction