Citation for published version (APA): Laarhoven, A. G. (2015). Pediatric immune thrombocytopenia: Catching platelets

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1 UvA-DARE (Digital Academic Repository) Pediatric immune thrombocytopenia: Catching platelets Laarhoven, Annemieke Link to publication Citation for published version (APA): Laarhoven, A. G. (2015). Pediatric immune thrombocytopenia: Catching platelets General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam ( Download date: 29 Nov 2017

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4 Pediatric Immune Thrombocytopenia Catching platelets Annemieke Gabriëlle Laarhoven

5 Annemieke G. Laarhoven, 2015 Cover: by Jessy Rietdijk, Subsoda Printing was generously supported by: Sanquin Research, Sanquin Plasma-producten, BD Biosciences, ITP Patiëntenvereniging ISBN: Layout: Johan Beekhuizen Printing: Gildeprint Drukkerijen, Enschede

6 Pediatric Immune Thrombocytopenia Catching platelets ACADEMISCH PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus prof. dr. D.C. van den Boom ten overstaan van een door het College voor Promoties ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel op vrijdag 30 januari 2015, te 14:00 uur door Annemieke Gabriëlle Laarhoven geboren te Laren, Nederland

7 Promotiecommissie Promotor: Copromotores: Overige leden: Faculteit: prof. dr. C.E. van der Schoot dr. M. de Haas dr. G. Vidarsson dr. M.C.A. Bruin prof. dr. R.A.W. van Lier prof. dr. T.W. Kuijpers prof. dr. S.M. van Ham dr. A.C. Lankester prof. dr. A.B.J. Prakken Geneeskunde

8 Contents Chapter 1 General Introduction 9 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Children with acute immune thrombocytopenia have normal numbers of FOXP3 regulatory T cells with enhanced function IgG Fc-receptors determine susceptibility for childhood immune thrombocytopenia, recovery and response to intravenous immunoglobulins Chronic Immune Thrombocytopenia in Children: a crosssectional study Functional platelet defects in children with severe chronic ITP as tested with two novel assays applicable for low platelet counts Chapter 6 General Discussion 147 Chapter 7 Summary Samenvatting List of publications PhD-Portfolio Curriculum Vitae Dankwoord

9 List of Abbreviations Ab Antibody ADCC Antibody-dependent cell-mediated cytotoxicity ADP Adenosine Diphosphate ALPS Autoimmune Lymphoproliferative Syndrome APC Antigen Presenting Cell Breg Regulatory B cell CFSE Carboxyfluorescein Diacetate Succinimidyl Ester CVID Common Variable Immune Deficiency C-ORF Classical Open Reading Frame CNV Copy Number Variation CPD Citrate-Phosphate-Dextrose CTLA4 Cytotoxic T lymphocyte Antigen 4 CVX Convulxin DC Dendritic Cell DMSO Dimethylsulfoxide EAE Experimental Autoimmune Encephalomyelitis FACS Fluorescence Activated Cell Sorting FcγR Fc gamma Receptor FcRn Neonatal Fc Receptor FOXP3 Forkhead box P3 GITR Glucocorticoid induced tumor necrosis factor receptor family related gene GPIbIX Glycoprotein IbIX GPIIbIIIa Glycoprotein IIbIIIa GPIV Glycoprotein IV HC Healthy Control HRQoL Health Related Quality of Life IFNγ Interferron gamma IL10 Interleukin 10 IL17 Interleukin 17 IVIg Intravenous Immunoglobulines JIA Juvenile Idiopathic Arthritis KIR Killer cell Immunoglobulin-like Receptor mab Monoclonal Antibody MAIPA Monoclonal Antibody Immobilization of Platelet Antigens

10 MFI MLPA MPS NC-ORF ND NK PAR-1 PBMC PIFT PMA PRP RA RTX SLE SNP SS Treg Teff TNFα TPO TRAP Treg vwf WAS XLT Median Fluorescence Intensity Multiplex Ligation-dependent Probe Amplification Mononuclear Phagocytic System Non-Classical Open Reading Frame Newly Diagnosed Natural Killer Proteinase Activated Receptor-1 Peripheral Blood Mononuclear Cells Platelet Immuno-Fluoresence Test Phorbol 12-Myristate 13-Acetate Platelet Rich Plasma Rheumatoid Arthritis Rituximab Systemic Lupus Erythematosus Single Nucleotide Polymorphism Sjögren s Syndrome Regulatory T cell Effector T cell Tumor Necrosis Factor Thrombopoietin Thrombin Receptor Activator Peptide Regulatory T cell von Willibrand Factor Wiskott-Aldrich Syndrome X-Linked Thrombocytopenia

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