University of Groningen Balance between herpes viruses and immunosuppression after lung transplantation Verschuuren, Erik A.M. IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2006 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Verschuuren, E. A. M. (2006). Balance between herpes viruses and immunosuppression after lung transplantation s.n. Copyright Other than for strictly personal use, 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), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 08-12-2018
Balance between Herpes Viruses and Immunosuppression after Lung Transplantation Studies on Epstein-Barr virus and Cytomegalovirus E.A.M. Verschuuren
Verschuuren, E.A.M. Balance between Herpes Viruses and Immunosuppression after Lung Transplantation Thesis Groningen with references with summary in Dutch Publication of this thesis was financially supported by: ABN/AMRO, Acthelion, Astellas, Novartis, Roche, Wyeth, Guide Cover: EBV Antigenemia of a lung transplant patient, or a result of a clumsy clinician in the laboratory causing a huge artefact. EBNA-1 = red, CD20 = green, nucleus = blue. Printed by: Gildeprint, Enschede, the Netherlands ISBN 90-367-2869-X ISBN 90-367-2870-3 digital version Copyright 2006 E.A.M. Verschuuren All rights reserved. No part of this book may be reproduced or transmitted, in any form or by any means, without written permission from the author.
RIJKSUNIVERSITEIT GRONINGEN Balance between Herpes Viruses and Immunosuppression after Lung Transplantation Studies on Epstein-Barr virus and Cytomegalovirus Proefschrift ter verkrijging van het doctoraat in de Medische Wetenschappen aan de Rijksuniversiteit Groningen op gezag van de Rector Magnificus, Dr. F. Zwarts, in het openbaar te verdedigen op woensdag 13 december 2006, om 13:15 uur Door Erik Alfons Maria Verschuuren Geboren op 19 februari 1962 te Breda
Promotores: Prof. Dr. C.G.M. Kallenberg Prof. Dr. G.H. Koëter Prof. Dr. J.M. Middeldorp Copromotores: Dr. W. van der Bij Dr. M.C. Harmsen Beoordelingscommissie: Prof. Dr. R.J.M. ten Berge Prof. Dr. Mw J.C. Kluin-Nelemans Prof. Dr. F. Miedema
Paranimfen: Dr. A. de Haan Dr. M.E. Erasmus
Contents Chapter Title Page 1 Aim and outline of this thesis. 9 2 Towards standardization of the human Cytomegalovirus antigenemia assay. 3 Effects of changing immunosuppressive regimen on the incidence, duration and viral load of Cytomegalovirus infection in renal transplantation: a single center report. 4 Direct quantification of human Cytomegalovirus immediateearly and late mrna levels in blood of lung transplant recipients by competitive nucleic acid sequence-based amplification. 5 Expression dynamics of human Cytomegalovirus immune evasion genes US3, US6, and US11 in the blood of lung transplant recipients. 6 Quantitative Epstein-Barr virus (EBV) Serology in Lung Transplant Recipients with primary EBV Infection and/or Post Transplant Lymphoproliferative Disease. 7 Dynamics and function of anti Epstein-Barr virus and anti Cytomegalovirus immune responses in the transplant patient: implications for immunosuppression. 8 Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of Post Transplant Lymphoproliferative Disease in high risk patients. 9 Treatment of Post-Transplant Lymphoproliferative Disease (PTLD) with Rituximab: the Remission, the Relapse and the Complication. 19 35 51 73 93 111 133 153 10 Epstein-Barr virus reactivation and lung transplant dysfunction. 165 11 Low rate of Bronchiolitis Obliterans Syndrome following Preemptive treatment of Post-Transplant Lymphoproliferative Disease after Lung Transplantation. 183
12 Epstein-Barr virus-dna load Monitoring Late after Lung Transplantation: A surrogate Marker of the Degree of Immunosuppression and a Safe Guide to Reduce Immunosuppression. 203 13 Summary and future perspective. 223 Nederlandse samenvatting 231 Dankwoord 235 Curriculum Vitae 239 List of publications 241