Bootcongres 2007. wetenschappelijke voorjaarsvergadering Nederlandse Transplantatie Vereniging

Bootcongres 2007 wetenschappelijke voorjaarsvergadering Nederlandse Transplantatie Vereniging 28 t/m 30 maart 2007 i.s.m. Leids Universitair Medisch Centrum Locatie: De Eemhof, Zeewolde

Inhoudsopgave Algemene informatie Welkomstwoord 3 Accreditatie 4 Informatie De Eemhof, zalen 5 Tijdstippen en locaties maaltijden 6 Bijeenkomsten voorafgaand en tijdens Bootcongres 6 Sponsors 7 Programma bootcongres en voordrachten Schematisch overzicht programma 8 Programma woensdag 9-11 Programma donderdag 12-19 Programma vrijdag 20-24 Samenvattingen gepresenteerde voordrachten 25-92 Overige ingezonden abstracts 93-136 Informatie NTV Organisatiecommissie Bootcongres 2007, colofon 137 Aanmeldingsformulier lidmaatschap NTV 138 Ruimte voor notities 139-144 In het programma vindt u achter de titel een verwijzing naar de pagina waar u het betreffende abstract kunt vinden. 2

Welkomstwoord Namens de Leidse organisatiecommissie heten wij u van harte welkom op het 19e Bootcongres van de Nederlandse Transplantatie Vereniging. Om het Bootcongres voor een ieder zo toegankelijk en attractief mogelijk te maken, is opnieuw gekozen voor een centrale locatie en parallelsessies. Uiteraard blijft bij toerbeurt een ander transplantatiecentrum als programma commissie eindverantwoordelijk voor de organisatie en couleur locale. Wij moedigen met name ook de leden, die de mogelijkheid hebben gekregen om één dag in te schrijven, aan hier optimaal gebruik van te maken. Wij zijn van mening, dat de organisatiecommissie er opnieuw in is geslaagd een interessant en representatief programma samen te stellen. De verschillende bloedgroepen binnen de Nederlandse transplantatiewereld (klinisch, basaal, paramedisch) zijn goed vertegenwoordigd en wij hopen op de voor het Bootcongres zo kenmerkende actieve participatie met levendige discussie en inhoudelijke kruisbestuiving. Door te kiezen voor alleen orale presentaties en het grote aantal inzendingen, kon helaas een aantal abstracts niet voor presentatie in aanmerking komen. Deze abstracts zijn wel in het programmaboek opgenomen. Daarnaast biedt het Bootcongres 2007 u verder o.a. een blik vooruit op stamcel therapie, een feestelijke NTS verjaardag met frisse blik op orgaan allocatie en ferme discussanten die voor en tegen donatie bij leven zullen pleiten. Niet in de laatste plaats is er ruimte voor sportieve inspanning en muzikale ontspanning. Een congres als dit kan niet georganiseerd worden zonder de hulp van vele medewerkers, die wij erkentelijk zijn voor hun inzet. Speciale dank gaat uit naar het secretariaat van de NTV, dat met enthousiasme zeer veel werk op efficiënte wijze heeft verricht. Ten slotte nog een woord van dank aan onze trouwe sponsors voor de onontbeerlijke steun. Op een aparte pagina worden deze farmaceutische firma's genoemd. Zij steunen de vereniging middels een meerjarige overeenkomst, waardoor de NTV dit congres en het klinisch najaarssymposium kan organiseren. Wij wensen u allen een vruchtbaar, interactief en vooral ook plezierig congres. Mede namens de Leidse organisatiecommissie, Hans de Fijter Frans Claas 3

Accreditatie Het bootcongres 2007 is geaccrediteerd door: Nederlandsche Internisten Vereeniging: Convent Medische Immunologie van de Nederlandse Vereniging voor Immunologie: Nederlands Genootschap van Maag-Darm-Leverartsen: Nederlandse Vereniging voor Heelkunde: 14 uur/punten 12 uur/punten 14 uur/punten 14 uur/punten Op individuele basis kan accreditatie worden aangevraagd bij: Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose Nederlandse Vereniging voor Cardiologie Nederlandse Vereniging voor Kindergeneeskunde 4

Algemene informatie De Eemhof De Eemhof Slingerweg 1 3896 LD Zeewolde Telefoon: 0900-33 33 64 6 Zalen Business Centre Grote zaal 250 personen theater 2 4 3 Parallelzaal 140 personen theater 1 2 1. Garderobe met kapstokken en bagage-opslag 2. Koffiebuffetten 3. Registratiebalie Bootcongres 4. Stand Eurotransplant 5

Locatie en tijdstippen van de maaltijden Ontvangst woensdag in Business Centre Lunch woensdag Market Restaurant Diner woensdag in Hamilton s Bar & Restaurant Ontbijt donderdag in Market Restaurant Lunch donderdag (lunchpakket i.v.m. spelprogramma) Diner donderdag in Hamilton s Bar & Restaurant Ontbijt vrijdag in Market Restaurant Lunch vrijdag in Market Restaurant 11.00-13.00 uur 12.00-13.00 uur 19.30-21.00 uur 07.00-08.30 uur 13.00-14.00 uur 19.30-21.00 uur 07.30-08.30 uur 13.00-14.00 uur Bijeenkomsten tijdens Bootcongres Woensdag 28 maart 2007 09.00 11.00 uur Landelijk overleg Levertransplantatie Locatie: Parallelzaal Business Centre 09.30 11.00 uur Landelijk overleg Niertransplantatie Locatie: Restaurant Saffraan 11.00 12.30 uur Transplantatie Werkgroep Nederland Locatie: Restaurant Saffraan 11.00 12.30 uur Landelijke Werkgroep Transplantatie Verpleegkunde Locatie: Parallelzaal Business Centre 6

Sponsors De Nederlandse Transplantatie Vereniging is de volgende sponsors zeer erkentelijk voor de ondersteuning van de diverse activiteiten tijdens het bootcongres: Hoofdsponsors Novartis Astellas Pharma Roche Wyeth Deelsponsor Genzyme Subsponsors Biotest Tepnel Lifecodes Fresenius Kabi 7

Schematisch overzicht programma woensdag 28 t/m vrijdag 30 maart 2007 Woensdag 28 maart 11.00 13.00 Aankomst van de gasten en registratie Business Centre 12.00 13.00 Lunch in Marketrestaurant Grote Zaal 13.00 15.00 Plenaire Sessie I 15.00 16.00 Ledenvergadering NTV 16.00 16.30 Theepauze, buffetten foyer 16.30 18.30 Plenaire Sessie II 18.30 19.30 Borrel aangeboden door Novartis 19.30 21.00 Diner Hamilton s Bar & Restaurant Donderdag 29 maart Zaal parallelsessies 08.30 10.30 Sessie III Parallelsessie Donatie 10.30 11.00 Koffiepauze, buffetten foyer 11.00 13.00 Sessie IV Parallelsessie Verpleegk. 13.00 14.00 Lunchpakket 14.00 16.30 Spelactiviteit in park 17.00 18.00 Plenaire sessie V Minisymposium NTS 10 jaar 18.00 19.00 Borrel aangeboden door NTS 19.30-21.00 Diner Hamilton s Bar & Restaurant en aansluitend feestavond Vrijdag 30 maart 08.30 10.30 Sessie VI Parallelsessie Lab 10.30 11.00 Koffiepauze buffetten foyer 11.00 13.00 Plenaire sessie VII incl. artikelprijs NTAB en Gauke Kootstra Prijs 13.00 14.00 Lunch in Marketrestaurant vertrek gasten 8

Plenaire sessie I woensdag 28 maart Voordrachten in het Nederlands, spreektijd 10 minuten, discussietijd 5 minuten. Voorzitters: Carla Baan en Maarten Christiaans 13.00 Prominent migration of IL-10 producing donor dendritic cells into the recipient after liver- but not kidney transplantation: implications for tolerance induction? (p. 25) B.M. Bosma 1, H.J. Metselaar 1, J.H. Gerrits 2, N.M. van Besouw 2, S. Mancham 1, H.W. Tilanus 3, E.J. Kuipers 1,2, J. Kwekkeboom 1. Depts of Gastroenterology and Hepatology 1, Internal Medicine 2 and Surgery 3, Erasmus MC, University Medical Center, Rotterdam, The Netherlands 13.15 Infectious complications after simultaneous pancreas-kidney transplantation: A role for the lectin pathway of complement activation (p. 26) J.J.W. Verschuren 1, A. Roos 1,2, M.J.K. Mallat 1, M.R. Daha 1, J.W. de Fijter 1, S.P. Berger 1. Depts of Nephrology 1 and Clinical Chemistry 2, Leiden University Medical Center, Leiden, The Netherlands 13.30 The effects of immunosuppressive drugs on in vitro stimulated B cells (p. 27) S. Heidt 1, D.L. Roelen 1, C. van Kooten 2, C. Eijsink 1, F.H.J. Claas 1, A. Mulder 1. Depts of Immunohaematology and Blood Transfusion 1 and Nephrology 2, Leiden University Medical Center, Leiden, The Netherlands 13.45 Successfull tapering of immunosuppression to low dose monotherapy steroids after living related HLA-identical renal transplantation (p. 28) J. van de Wetering, J. H. Gerrits, N. M. van Besouw, J. van Gestel, W. Weimar. Dept of Internal Medicine and Transplantation, Erasmus MC, University Hospital Rotterdam, Rotterdam, The Netherlands 14.00 Characterization of natural Tregs in non-human primates (p. 29) K. Haanstra, M. Jonker. Biomedical Primate Research Centre, Rijswijk, The Netherlands 9

Plenaire sessie I vervolg woensdag 28 maart 14.15 Should the mycophenolate mofetil dose be based on total or unbound mycophenolic acid exposure when renal function is impaired or when albumin levels are low? (p. 30) R.M. van Hest 1, T. van Gelder 1,2, A.G. Vulto 1, L.M. Shaw 3 and R.A. Mathot 1. Depts of Clinical Pharmacology 1 and Internal Medicine 2, Erasmus MC, Univeristy Medical Center, Rotterdam, The Netherlands and Dept of Pathology & Laboratory Medicine 3, University of Pennsylvania, Philadelphia, USA 14.30 Identification of 3 novel non-hla target Antigens recognized after Kidney Transplantation (p. 31) H.G. Otten 1, M. van Loon 1, W.G.J. van Ginkel 1, E.A. van de Graaf 2 and R.J. Hené 3. Depts of Immunology 1, Heart-Lung Center Utrecht 2 and Nephrology 3, University Medical Center, Utrecht, The Netherlands 14.45 The virtual PRA (Panel Reactive Antibody value): An excellent tool to predict the chance to find a crossmatch negative donor (p. 32) I.I.N. Doxiadis 1,2, G.W. Haasnoot 2, M.D. Witvliet 2, F.H.J. Claas 1,2. Eurotransplant Reference Laboratory 1 and Dept of Immuno-haematology and Blood Transfusion 2, Leiden University Medical Center, Leiden, The Netherlands 15.00 Ledenvergadering Nederlandse Transplantatie Vereniging 16.00 Theepauze Plenaire sessie II woensdag 28 maart Voorzitters: Luuk Hilbrands en Dave Roelen 16.30 Biology of mesenchymal stem cells Gastspreker: Prof. dr. W.E. Fibbe, afdeling IHB, LUMC, Leiden 10

Plenaire sessie II vervolg woensdag 28 maart Voordrachten in het Nederlands, spreektijd 10 minuten, discussietijd 5 minuten 17.15 The effect of one random protocol blood transfusion on immunization and graft survival in renal transplantation (p. 33) J. Aalten 1, S.P.M. Lems 2, F.H.J. Claas 3, N. Lardy 4, P.M. van den Berg- Loonen 5, W.A. Allebes 6, A.J. Hoitsma 1. Depts of Nephrology 1, Transplantation Immunology 6, Radboud University Medical Centre Nijmegen, Transplantation Immunology 2, University Medical Centre Groningen, Groningen, Immunohematology and Blood Transfusion 3, Leiden University Medical Centre, HLA Diagnostics, Sanquin Diagnostics at CLB 4, Amsterdam and Tissue Typing Laboratory 5, University Hospital Maastricht, The Netherlands 17.30 Myeloid and plasmacytoid dendritic cell subsets in human kidney during allograft rejection (p. 34) K. Zuidwijk 1, J.W. de Fijter 1, M.J.K. Mallat 1, M. Eikmans 2, I. Bajema 2, C. van Kooten 1. Depts of Nephrology 1 and Pathology 2, Leiden University Medical Center, Leiden, The Netherlands 17.45 Intrarenal CD20+ cells do not predict clinical outcome in acute renal allograft rejection (p. 35) C.G. Scheepstra 1, F.J. Bemelman 2, C.M. van der Loos 1, J.J. Weening 1, R.J. ten Berge 2, S. Florquin 1. Depts of Pathology 1, Academic Medical Center, Amsterdam and Nephrology and Clinical Immunlogy 2, Academic Medical Center, Amsterdam, The Netherlands 18.00 Mesenchymal stem cells expanded from human transplanted heart regulate donor specific immune responses (p. 36) M.J. Hoogduijn 1, M.J. Crop 1, A.M.A. Peeters 1, A.H.M.M. Balk 2, A.P.W.M. Maat 2, W. Weimar 1, C.C. Baan 1. Depts of Internal Medicine 1 and Thoracic Center 2, Erasmus MC, University Medical Center, Rotterdam, The Netherlands 18.15 Still better after all these years (p. 37) W. Weimar 1, W. Zuidema 1, J. Roodnat 1, I. Alwayn 2, J. IJzermans 2. Depts of Internal Medicine 1 and General Surgery 2, Erasmus MC, University Medical Center, Rotterdam, The Netherlands 18.30 Borrel 19.00 Diner 11

Sessie III donderdag 29 maart Voordrachten in het Nederlands, spreektijd 10 minuten, discussietijd 5 minuten. Voorzitters: Stefan Berger en Luuk van der Laan 8.30 Intravenous immunoglobulins reduce allogeneic T-cell activation after liver transplantation by modulating the interaction between Dendritic Cells and Natural-Killer cells (p. 38) T. Tha-In 1, J. Kwekkeboom 1, H.W. Tilanus 2, Z.M.A. Groothuismink 1, M. van Hagen 3, G. Kazemier 2, E.J. Kuipers 1, R.A. de Man 1, H.J. Metselaar 1. Depts of Gastroenterology and Hepatology 1, Surgery 2 and Internal Medicine 3, Erasmus MC, University Medical Center, Rotterdam, The Netherlands 8.45 Single high dose ATG F or five doses daclizumab equally reduce acute rejection rates after simultaneous pancreas kidney transplantation (p. 39) P. van der Linde 1, P.J.M. van de Boog 2, I.N. Doxiadis 3, C. van Kooten 2, B.O. Roep 3, S.P. Berger 2, F.H.J. Claas 3, J. Ringers 1 J.W. de Fijter 2. Department of Surgery 1, of Nephrology 2 and Immunohematology and Blood Transfusion 3, Leiden University Medical Center, Leiden, The Netherlands 9.00 Cumulative negative effects of donor brain death and subsequent ischemia/reperfusion on kidney graft injury and function (p. 40) W.N. Nijboer 1, T.A. Schuurs 2, B. Swart 2, P.J. Ottens 2, H.G.D. Leuvenink 2, R.J. Ploeg 1. Departments of Surgery 1, Surgical Research Laboratory 2, University Medical Center Groningen, The Netherlands 9.15 Estimation of graft survival and risk of delayed graft function in recipients of deceased donor kidneys: development of regression models based on donor age (p. 41) C. Moers 1, N.S.S. Kornmann 1, H.G.D. Leuvenink 1, R.J. Ploeg 1. Dept of Surgery 1, University Medical Center Groningen, The Netherlands 9.30 Dry powder inhalation of cyclosporine a in rats: pharmacokinetics and effectiveness in rejection prevention in lung transplantation (p. 42) G.S. Zijlstra, M.J. Wolting, A.H. Petersen, J. Prop, W. van der Bij, H.A.M. Kerstjens, W.L.J. Hinrichs, H.W. Frijlink. Pharmaceutical Technology and BioPharmacy, University of Groningen, Groningen, The Netherlands 12

Sessie III vervolg donderdag 29 maart 9.45 Luminex crossmatches are as sensitive as flow cytometric crossmatches (p. 43) P.M. van den Berg-Loonen 1, E.V.A. Billen 1, G.M.S.J. Tjon 1, C. Heylen 2, C.E.M. Voorter 1. Tissue Typing Laboratory 1, University Hospital Maastricht, Maastricht, The Netherlands, Tepnel Lifecodes 2, Nijlen, Belgium 10.00 Interleukin-6 mediates early renal ischemia-reperfusion injury in humans (p. 44) D.K. de Vries 1,2, A.F.M. Schaapherder 1, J. van Pelt 2, J.H.N. Lindeman 1. Departments of Surgery 1 and Clinical Chemistry 2, Leiden University Medical Center, Leiden, The Netherlands 10.15 Conversion to steroid free rapamycin monotherapy leads to expansion of CD4 + CD25 bright+ FoxP3 T-cells in renal transplant patients (p. 45) T. Hendrikx 1, E. van Gurp 1, W. Schoordijk 1, M. Klepper 1, J. Velthuis 1, A. Geel 1, J. IJzermans 2, W. Weimar 1, C. Baan 1. Departments of Internal Medicine 1 and Surgery 2, Erasmus MC, University Medical Center, Rotterdam, The Netherlands 10.30 Koffiepauze Parallelsessie Donatie donderdag 29 maart Voorzitters: Jeanette Doornink en Frank van Duin 8.30 Capita selecta: non-heart beating organen Gastspreker: Dr. R.J. Porte, chirurg, UMC Groningen Voordrachten in het Nederlands, spreektijd 7 minuten, discussietijd 3 minuten. 9.00 Non Heart Beating Multi Organ Donation: Lung donation (p. 46) D.M. Nijkamp 1, W. van der Bij 2, E.A.M. Verschuuren 2, M.E. Erasmus 3. Depts of Surgery, Section Organ Donation 1, Pulmonary diseases and lung transplantation 2 and Cardiothoracic Surgery and lung transplant-ation 3. University Medical Center Groningen, The Netherlands 13

Parallelsessie Donatie vervolg donderdag 29 maart 9.10 Kwaliteitsvergelijking tussen geïmporteerde en geëxporteerde nieren in Nederland (p. 47) E. de Buijzer 1, M.B.A. Heemskerk 1, A. Hoitsma 2, M. Christiaans 3. Orgaancentrum, Nederlandse Transplantatiestichting 1, Leiden, Afdeling Nierziekten 2, Radboud Universiteit, Nijmegen en Afdeling Interne Geneeskunde 3, Academisch Ziekenhuis Maastricht, The Netherlands 9.20 Are the Dutch criteria for accepting donor hearts too strict? (p. 48) J.A.M. Hagenaars 1, P.J. Batavier 2, A.H.M.M. Balk 3, N. de Jonge 2. Depts of Surgery 1, Erasmus MC, Rotterdam, Heart-Lung center 2, University Hospital Utrecht, Utrecht and Cardiology 3, Erasmus MC, Rotterdam, The Netherlands 9.30 A comparison of left sided versus right sided hand-assisted laparoscopic donor (p. 49) R.C. Minnee 1, W.A. Bemelman 1, P.J. van Koperen 1, S.W. Polle 1, F.J. Bemelman 2, D.J. Gouma 1, M.M. Idu 1. Dept of Surgery 1 and Nefrology 2, Academic Medical Center, Amsterdam, The Netherlands 9.40 Consent for donation in The Netherlands: relation between registration and relatives consent (p. 50) H.A. van Leiden 1, N.E. Jansen 1, B.J.J.M. Haase-Kromwijk 1, M.B.A. Heemskerk 1, C.R. Smand 1, E. de Buijzer 1, A.J. Hoitsma 1. Dutch Transplant Foundation 1, Leiden, The Netherlands 9.50 Psychological barriers in living kidney donation (p. 51) L. Kranenburg 1, W. Zuidema 2, W. Weimar 2, M. Hilhorst 3, J.N.M. IJzermans 4, J. Passchier 1, J. Busschbach 1. Depts of Medical Psychology & Psychotherapy 1, Internal Medicine 2, Medical Ethics 3 and Surgery 4, Erasmus University Medical Center, Rotterdam, The Netherlands 10.00 Screening living-related liver transplantation donors (p. 52) H. Telleman 1, L. Elshove 1, H.W. Tilanus 2, J.H.P. Wilson 3, M. Buijk 1, H.J. Metselaar 1, G. Kazemier 2. Depts of Gastroenterology 1, Surgery 2 and Internal Medicine 3, Erasmus Medical Center, Rotterdam, The Netherlands 10.10 Domino Paired Kidney Donation with altruistic donors (p. 53) W. Zuidema 1, L. Kranenburg 2, R. Erdman 2 M. de Klerk 1, M. Hilhorst 3, J.N.M. IJzermans 4, W. Weimar 1. Depts of Internal Medicine 1, Medical Psychology & Psychotherapy 2, Medical Ethics 3 and General Surgery 4, Erasmus MC, University Medical Center, Rotterdam, The Netherlands 14

10.20 Einde programma / Koffiepauze Parallelsessie Transplantatieverpleegkundigen donderdag 29 maart Voorzitters: Marjo van Helden en Rietje Liedmeyer 11.00 De Intermed-methode: integrale zorg voor de chronische zieke patiënt Gastspreker: Dr. F.J. Huijse, UMCG, Groningen Voordrachten in het Nederlands, spreektijd 7 minuten, discussietijd 3 minuten. 11.30 Implications of living donor screening (p. 54) J.A. Kal-van Gestel 1, M.A.A. van Noord 1, W. Zuidema 1, J.N.M. IJzermans 2, W. Weimar 1. Depts of Internal Medicine, Section Transplantation 1 and General Surgery 2, Erasmus MC, University Medical Center, Rotterdam, The Netherlands 11.40 Motivations of altruistic living kidney donors (p. 55) W. Zuidema 1, L. Kranenburg 2, N. Tronchet 3, M. Hilhorst 4, R. Erdman 2, J.N.M. IJzermans 4, W. Weimar 1. Depts of Internal Medicine 1, Medical Psychology & Psychotherapy 2, Social Work 3, Medical Ethics 4 and General Surgery 5, Erasmus MC, Rotterdam, The Netherlands 11.50 Q-methodology to identify young renal transplant recipients at risk for non-compliance (p. 56) M.Tielen¹, A.L. van Staa², S. Jedeloo², W. Weimar¹. Depts of Internal Medicine 1, Erasmus MC, University Medical Centre, Rotterdam and Rotterdam College 2, Expertise Centre Transitions in Care, Rotterdam, The Netherlands 12.00 Current health status and quality of life of adult patients who have survived more than 15 years after liver transplantation (p. 57) G. Drent 2, L. de Kroon 2, A.P. van den Berg 2, E.B. Haagsma 1. Liver Transplant Group Groningen 1 and dept of Gastroenterology and Hepatology 2, University Medical Center Groningen, University of Groningen, The Netherlands 15

Parallelsessie Transplantatieverpleegkundigen donderdag 29 maart 12.10 Heeft zwangerschap een negatieve invloed op de niertransplantaatfunctie? (p. 58) M. van Helden, A. Hoitsma. Dept of Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen 12.20 Beroepsdeelprofiel transplantatieverpleegkundige (p. 59) S.F.J. de Kruijf-Bazen 1, H.J.A. Dackus 1, P.T.R. Ulrichts 1. Afdeling Interne Geneeskunde / Nefrologie 1, Academisch Ziekenhuis Maastricht, The Netherlands 12.30 Cognitieve emotionele regulatie van patiënten die wachten op een levertransplantatie (p. 60) L. Elshove, A. Wilschut, J. Gutteling, H.J. Metselaar, afdeling Maag-, Darm- en Leverziekten, Erasmus Medisch Centrum, Rotterdam 12.40 Symptom experience associated with side effects of immunosuppressive therapy in lung transplant recipients (p. 61) D.S. Bosscher¹, P. Moons², E.A.M. Verschuuren¹, W. van der Bij¹. Dept of Internal Disease 1, University Medical Centre Groningen, The Netherlands. Centre for Health Services and Nursing Research 2, School of Public Health, Faculty of Medicine, KU-Leuven, Belgium 12.50 Einde programma 13.00 Lunch 14.00 Ontspanning 16

Sessie IV donderdag 29 maart Voordrachten in het Nederlands, spreektijd 10 minuten, discussietijd 5 minuten. Voorzitters: Teun van Gelder en Sandro Schaapherder 11.00 Modulation of allograft rejection by dexamethasone-treated rat dendritic cells (p. 62) A.M. Stax, C. Crul, M.C. Essers, S.W.A. Kamerling, A.M. Woltman, C. van Kooten. Dept of Nephrology, Leiden University Medical Centre, Leiden, The Netherlands 11.15 Improved dose prediction of tacrolimus in de novo kidney transplant patients with population pharmacokinetic modelling including genetic polymorphisms (p. 63) R.R. Press 1, B.A. Ploeger 2,3, J. den Hartigh 1, R.J.H.M. van der Straaten 1, J. van Pelt 1, M. Danhof 2, J.W. de Fijter 1, H.J. Guchelaar 1. 1 Clinical Pharmacy and Toxicology, Nephrology, Clinical Chemistry, Leiden University Medical Center; 2 Leiden Amsterdam Center for Drug Research and 3 Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics, The Netherlands 11.30 Combining allo-antigen specific and polyclonal stimulation methods to obtain high numbers of antigen-specific CD4+CD25+ Treg for immunotherapy (p. 64) J. Peters 1, H. Koenen 1, L. Hilbrands 2, I. Joosten 1. Depts of Bloodtransfusion and Transplantation Immunology 1 and Nephrology 2, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands 11.45 Living donor liver transplantation, the first results in adult recipients in The Netherlands (p. 65) J. de Jonge, L. Elshove, H.W. Tilanus, H.J. Metselaar, K.T. Tran, Th.N. Groenland, G. Kazemier. Depts of Hepatology and Surgery, Erasmus Medical Center Rotterdam, The Netherlands 12.00 Improved cold storage preservation of porcine kidney grafts using Polysol (p. 66) M.C.J.M. Schreinemachers 1, B.M. Doorschodt 1, R.H. Tolba 2, T.M. van Gulik 1. Dept of Surgery (Surgical Laboratory) 1, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and House of Experimental Therapy 2, University of Bonn, Bonn, Germany 17

Sessie IV vervolg donderdag 29 maart 12.15 The role of historical donor specific HLA antibodies in renal transplantation (p. 67) I.I.N. Doxiadis 1,2, G.W. Haasnoot 2, J.W. de Fijter 3,G.G. Persijn 4, F.H.J. Claas 1,2. Eurotransplant Reference Laboratory 1 and Depts of Immunohaematology and Blood Transfusion 2, Nephrology 3, Leiden University Medical Center and Eurotransplant International Foundation 4, Leiden, The Netherlands 12.30 Characterization of T-cells located in arterial walls with Cardiac Allograft Vasculopathy (p. 68) E. de Koning 1, M.C. Hagemeijer 1, D.F. van Wichen 1, J. van Kuik 1, M.F.M. van Oosterhout 1, N. de Jonge 2, J. Lahpor 2, F.H.J. Gmelig-Meyling 3, R.A. de Weger 1. Depts of Pathology 1, Heart Lung Center 2 and Immunology 3, University Medical Center, Utrecht, The Netherlands 12.45 De waarde van pathologische beoordeling van oude non-heartbeating donornieren vóór transplantatie (p. 69) M.G.J. Snoeijs 1, W.A. Buurman 1, M.H.L. Christiaans 2, J.P. Van Hooff 2, R.J. van Suylen 3, C.J. Peutz-Kootstra 3, L.W.E. van Heurn 1. Depts of Surgery 1, Nephrology 2 and Pathology 3, University Hospital Maastricht, Maastricht, The Netherlands 13.00 Lunch 14.00 Ontspanning 18

Plenaire Sessie V - Minisymposium NTS donderdag 29 maart Voorzitter: Willem Weimar Minisymsposium ter gelegenheid van het 10-jarig bestaan Nederlandse Transplantatie Stichting 17.00 'Developments in Donor Management' Dr. P. Schnuelle, Universiteitskliniek Heidelberg, Duitsland 'Allocatie in Nederland: Terugblik en Toekomst' 17.30 Prof. dr. F.H.J. Claas, Nationaal Referentie Laboratorium Leiden 17.45 Prof. dr. A.J. Hoitsma, UMC Radboud Nijmegen/NTS 18.00 Einde programma, aansluitend borrel, aangeboden door de NTS 19

Sessie VI vrijdag 30 maart Voordrachten in het Nederlands, spreektijd 8 minuten, discussietijd 4 minuten. Voorzitters: Frederike Bemelman en Eltjo de Maar 8.30 Successful steroid withdrawal after renal transplantation: 6 years follow-up (p. 70) M.A.C.J. Gelens 1, M.H.L. Christiaans 1, J.P. van Hooff 1. Dept of Internal Medicine 1, University Hospital Maastricht, The Netherlands 8.42 Tacrolimus pharmacodynamics in HIV positive recipients listed for a renal transplantation (p. 71) R.J. Hené, C. van Kesteren, K. Schurink, T. Ververs. Depts of Pharmacy, Internal Medicine and Infectious Diseases and Nephrology, University Medical Centre, Utrecht, The Netherlands 9.54 Body Mass Index pre-renal transplantation is a U-shaped risk factor for graft failure and death (p. 72) E.K. Hoogeveen 1, J. Aalten 2, M. Mallat 1, J.I. Roodnat 3, G. Borm 4, A.J. Hoitsma 2, J.W. de Fijter 1. Depts of Nephrology 1, Leiden University Medical Center, Leiden, Nephrology 2, Radboud University Medical Center, Nijmegen, Nephrology 3, Erasmus MC, University Medical Center, Rotterdam and Epidemiology and Biostatistics 4, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands 9.06 Influence on clinical outcome of Luminex DDA antibodies in pretransplant sera of patients transplanted in the AM program (p. 73) P.M. van den Berg-Loonen 1, G.M.S.J. Tjon 1, C.E.M. Voorter 1, E. van Heurn 2, M.H.L. Christiaans 3, F.H.J. Claas 4, J.P. van Hooff 3. Tissue Typing Laboratory 1, Departments of Surgery 2 and Internal Medicine 3, University Hospital Maastricht and Immunohaematology and Bloodbank 4, Leiden University Medical Center, Leiden, The Netherlands. 9.18 A Prospective Randomized Study Comparing Minimal Invasive Open and Hand Assisted Laparoscopic Living Donor Nephrectomy (p. 74) H.S. Hofker, W.N. Nijboer, C. Krikke, J. Niesing, J.J. Homan van de Heide, E.F. de Maar, M. Seelen, W.J. van Son, G. Navis, R.J. Ploeg. University Medical Centre Groningen, The Netherlands 20

Sessie VI vervolg vrijdag 30 maart 9.30 Concentration-controlled systemic exposure provides improved safety after CNI or MMF withdrawal (p. 75) J.S. Mourer 1, J. den Hartigh 2, M.J. Mallat 1, S.P. Berger 1, J.W. de Fijter 1. Department of Nephrology 1 and Clinical Pharmacology and Toxicology 2, Leiden University Medical Center, Leiden, The Netherlands 9.42 Pre Transplant Soluble CD30 is a stronger Predictor of the Bronchiolitis Obliterans Syndrome than Anti-HLA Antibodies occurring after Lung Transplantation (p. 76) J.M. Kwakkel-van Erp 1, H.G. Otten 2, G.D. Nossent 1, D.A. van Kessel 3, W.G. van Ginkel 2, J.M.M. van den Bosch 3, E.A. van de Graaf 1. Depts of Pulmonology 1, Immunology 2, Academic Medical Centre Utrecht and Pulmonology 3, Sint Antonius Ziekenhuis, Nieuwegein, The Netherlands 9.54 The influence of HLA-DR mismatching on long-term outcome of lung transplantation is masked by a new immunosuppressive protocol (p. 77) W. van der Bij, E.A.M. Verschuuren, M.E. Erasmus, S.P.M. Lems, B.G. Hepkema. University Medical Centre Groningen, Groningen, The Netherlands 10.06 Niertransplantaties van gecontroleerde en ongecontroleerde nonheart-beating donoren hebben vergelijkbare resultaten (p. 78) M.G.J. Snoeijs 1, A.C.P. Sewing 1, M.H. Christiaans 2, J.P. Van Hooff 2, E.M. van den Berg-Loonen 3, W.A. Buurman 1, L.W.E. van Heurn 1. Depts of Surgery 1, Nephrology 2 and HLA Typing Laboratory 3, University Hospital Maastricht, The Netherlands 10.18 Higher Body Mass Index is associated with higher Filtration Fraction after Living Kidney Donation (p. 79) M. Rook, R. Bosma, W. van Son, S. Hofker, J. Homan van der Heide, R. Ploeg, G. Navis. University Medical Center Groningen, The Netherlands 10.30 Koffiepauze 21

Parallelsessie Laboratorium vrijdag 30 maart Voordrachten in het Nederlands, spreektijd 8 minuten, discussietijd 4 minuten. Voorzitters: Hans Koenen en Jaap Kwekkeboom 8.30 Immune monitoring reveals intact regulatory capacities of CD4+CD52bright+ T-cells of renal allograft recipients treated with the JAK-3 inhibitor CP-690,550 (p. 80) C. Baan 1, E. van Gurp 1, M. Klepper 1, W. Schoordijk 1, G. Chan 2, W. Weimar 1. Depts of Internal Medicine 1, Erasmus MC, Rotterdam, The Netherlands and Clinical R&D Pfitzer 2, USA 8.42 Differentiation of regulatory T cells is controled by the level of T cell receptor triggering, costimulation and cytokine signalling (p. 81) H.J.P.M. Koenen, E. van Rijssen, E. Fasse, I. Joosten. Dept of Bloodtransfusion and Transplantation Immunology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands 8.54 Changes in frequency and phenotype of circulating CD4 + Foxp3 + regulatory T cells after conversion from calcineurin inhibitor to mycophenolate mofetil monotherapy (p. 82) A. Demirkiran 1, V.D.K.D. Sewgobind 1,2, H.J. Metselaar 3, J. van der Weijde 1, A. Kok 1, C.C. Baan 2, G. Kazemier 1, H.W. Tilanus 1 and L.J.W. van der Laan 1. Depts of Surgery 1, Internal Medicine 2 and Gastroenterology and Hepatology 3, Erasmus MC, University Medical Center, Rotterdam, The Netherlands 9.06 The influence of KIR genes and HLA-C/Bw4 epitopes on the outcome of HLA identical stem cell transplantation (p. 83) W.T.N. Swelsen 1, J.J.W.M. Janssen 2, O. Visser 2, A.R. Jonkhoff 2, N.M. Lardy 1. Depts of HLA Diagnostics 1, Sanquin and Haematology 2, VU, Free University Medical Centre, Amsterdam, The Netherlands 9.18 Vitamin D3 does not prevent LPS-induced activation of rat bone marrow-derived dendritic cells (p. 84) C. Crul, A.M. Stax, A.M. Woltman, C. van Kooten. Dept of Nephrology, Leiden University Medical Center, Leiden, The Netherlands 22

Parallelsessie Laboratorium vrijdag 30 maart 9.30 Dendritic cells in hepatic lymph nodes are exhausted and have a poor allogeneic T-cell stimulatory capacity (p. 85) B.M. Bosma¹, P.P.C. Boor¹, H.W. Tilanus 2, T.C.K. Tran 2, J.N.M. IJzermans 2, E.J. Kuipers¹, H.J. Metselaar¹, J. Kwekkeboom¹. Depts of Gastroenterology and Hepatology 1 and Surgery 2, Erasmus MC, University Medical Center, Rotterdam, The Netherlands 9.42 Activation using combinations of toll-like receptor ligands and CD40L can enhance the regulatory function of human dendritic cells (p. 86) E. Csomor 1, S. van der Kooij 1, C. van Kooten 1. Dept of Nephrology 1, Leiden University Medical Center, Leiden, The Netherlands 9.54 Rapamycin reduces the capacity of plasmacytoid dendritic cells to induce IL10-producing regulatory T-cells (p. 87) P.P.C Boor, H.J. Metselaar, J. Kwekkeboom. Dept of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands 10.06 Immunological monitoring of renal transplant patients to identify patients at risk for acute rejection following reduction of immunosuppression (p. 88) E. Kreijveld 1, H. Koenen 1, B. van Cranenbroek 1, E. van Rijssen 1, L. Hilbrands 2, I. Joosten 1. Depts of Bloodtransfusion and Transplantation Immunology 1 and Nephrology 2, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands 10.18 High FOXP3 mrna expression levels in the graft, but not in the peripheral blood, are associated with acute rejection in heart transplant patients (p. 89) E. Dijke 1, K. Caliskan 2, S. Korevaar 1, A. Balk 2, P. Zondervan 3, L. Maat 4, W. Weimar 1, C. Baan 1. Depts of Internal Medicine 1, Cardiology 2, Pathology 3 and Thoracic Surgery 4, Erasmus MC, University Medical Center, Rotterdam, The Netherlands 10.30 Koffiepauze 23

Plenaire sessie VII vrijdag 30 maart Voordrachten in het Nederlands, spreektijd 10 minuten, discussietijd 5 minuten. Voorzitters: Irma Joosten en Cees van Kooten 11.00 Low mannose-binding lectin levels are associated with superior graft and patient survival after simultaneous pancreas kidney transplantation (p. 90) S.P. Berger 1, A. Roos 1,2, M.J.K. Mallat 1, A.F.M. Schaapherder 3, I.I. Doxiadis 4, C. van Kooten 1, M.R. Daha 1, J.W. de Fijter 1. Depts of Nephrology 1, Clinical Chemistry 2, Surgery 3 and Immunohematology and Bloodtransfusion 4, Leiden University Medical Center, Leiden, The Netherlands 11.15 Donor-specific T-cell reactivity during steroid monotherapy after HLA-identical living-related kidney transplantation (p. 91) J.H. Gerrits, J. van de Wetering, W. Weimar, N.M. van Besouw. Internal Medicine - Transplantation, Erasmus MC, University Medical Center, Rotterdam, The Netherlands 11.30 Calculation of survival from the first day of renal replacement therapy (RRT) justifies propoganda for pre-emptive transplantation (p. 92) W. Weimar 1, J. Homan van der Heide 1, H. de Fijter 1, J. Surachno 1, R. Hené 1, M. Christiaans 1, F. de Charro 2, A. Hoitsma 1. Dutch Organ Transplant Registry and the Dutch Renal Transplant Centres 1 and Dutch Registry for Renal Replacement Therapy 2, The Netherlands 11.45 Pro-con sessie Donatie bij leven Prof. dr. A.J. Hoitsma vs Drs. M. Bos 12.30 Uitreiking Novartisprijs 12.45 Uitreiking Gauke Kootstra Prijs, gevolgd door voordracht van de prijswinnaar 13.00 Lunch 14.00 Vertrek deelnemers 24

Prominent migration of IL-10 producing donor dendritic cells into the recipient after liver- but not kidney transplantation: implications for tolerance induction? B.M. Bosma 1, H.J. Metselaar 1, J.H. Gerrits 2, N.M. van Besouw 2, S. Mancham 1, H.W. Tilanus 3, E.J. Kuipers 1,2, J. Kwekkeboom 1. Depts of Gastroenterology and Hepatology 1, Internal Medicine 2 and Surgery 3, Erasmus MC, University Medical Center, Rotterdam, The Netherlands Introduction: The role of chimerism in tolerance induction after transplantation is still under debate. Since dendritic cells (DC) are the most potent antigenpresenting cells, chimerism of these cells is likely to regulate the balance between tolerance and rejection. We compared DC chimerism after liver transplantation (LTx) and kidney transplantation (RTx), and studied the functional properties of DC that detach from liver grafts during pre-transplant perfusion. Materials and Methods: The presence of donor CD1c + CD20 - DC in blood of transplant recipients was established by flowcytometric analysis using HLA-A2 mismatches between donor and recipient. DC were isolated from liver graft perfusates collected at the end of the cold storage period (n=7), and from blood of healthy individuals (n=7), and their cytokine production and allogeneic T-cell stimulatory capacity were compared. Results: In liver graft recipients (n=11) donor DC made up 4.2% (range 0.0-18.1%) of total circulating DC on day 1, and 0.6% (range 0.0-1.3%) on day 5 post-ltx. In contrast, on day 1 post-rtx (n=6) only 0.3% (range 0.0-1.1%) of circulating DC were of donor origin (LTx versus RTx: p=0.015). During pretransplant perfusion high numbers of donor DC (0.9 x10 6 ; range 0.1-4.5 x10 6 ) detached from liver grafts. Freshly isolated liver perfusate DC were able to stimulate allogeneic T-cell proliferation. Upon stimulation with LPS, liver DC produced significantly higher amounts of IL-10 than blood DC (1.9±0.6 versus 0.15±0.05 ng/ml: p=0.006), but no IL-12. Likewise, upon stimulation with poly (I:C) and IFNγ liver DC produced 19 times more IL-10 (1.3±0.8 ng/ml) than IL- 12 (0.07±0.03 ng/ml; p= 0.029), while blood DC produced low amounts of both cytokines (0.1±0.07 and 0.09±0.04 ng/ml, respectively; p=0.47). Conclusion: After LTx, but not RTx, considerable numbers of donor-derived DC migrate from the donor graft via the blood circulation into the recipient. These DC strongly produce the immune-regulatory cytokine IL-10, but very little of the T-helper1 driving cytokine IL-12. Migration of these donor DC may contribute to lower immunogenicity of liver grafts in comparison with kidney grafts. 25

Infectious complications after simultaneous pancreas-kidney transplantation: A role for the lectin pathway of complement activation J.J.W. Verschuren 1, A. Roos 1,2, M.J.K. Mallat 1, M.R. Daha 1, J.W. de Fijter 1, S.P. Berger 1. Depts of Nephrology 1 and Clinical Chemistry 2, Leiden University Medical Center, Leiden, The Netherlands Introduction: Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice for many patients with diabetes mellitus type 1 and end stage diabetic nephropathy. However this procedure is characterized by a high rate of infectious complications. The innate immune system may play a prominent role in antimicrobial defence in immunocompromised patients. Mannose-binding lectin (MBL) is a recognition molecule of the lectin pathway of complement activation and serum levels are largely determined by frequently occurring polymorphisms of the MBL gene. We questioned whether MBL deficiency influences infectious complications after SPKT. Methods: Infectious complications in the first year after transplantation were retrospectively scored in 162 consecutive SPKT patients who received their transplant at our center between 1990 and 2005. Pre-transplant serum MBL levels were determined by ELISA. Results: Clinically relevant infections were seen in 91.3% of the patients. Overall mean infection rate was 3.46 infections/patient in the first year after SPKT. The overall risk for infectious complications decreased with increasing baseline MBL levels (P = 0.041). More specifically, every 500 ng/ml increase in baseline MBL was associated with a relative risk of 0.93 (P = 0.041) for urinary tract infections and a relative risk of 0.68 (P= 0.029) for urosepsis. Urosepsis was significantly more common in patients with low baseline MBL (<350 ng/ml) compared to higher MBL levels (22.5% vs. 9.0%, P = 0.024). No significant influence of MBL on the occurrence of wound infections and CMV disease was demonstrated. Low MBL was not associated with increased infection-related mortality. Conclusions: With the current study we show that high levels of serum MBL protect against urinary tract infections and more specifically against urosepsis after SPKT. These data indicate an important role of the lectin pathway in antimicrobial defence in immunocompromised transplant recipients. 26

The effects of immunosuppressive drugs on in vitro stimulated B cells S. Heidt 1, D.L. Roelen 1, C. van Kooten 2, C. Eijsink 1, F.H.J. Claas 1, A. Mulder 1. Depts of Immunohaematology and Blood Transfusion 1 and Nephrology 2, Leiden University Medical Center, Leiden, The Netherlands Humoral immunity is increasingly recognized as an important factor in the rejection of organ transplants. While current immunosuppressive drugs are mainly focused on inhibition of T cell immunity, their effect on B cell immunity is largely unknown. We studied the effects of immunosuppressive drugs on purified, in vitro stimulated B cells. Immunomagnetically purified CD19 + B cells from healthy volunteers were stimulated with either accessory cells expressing CD40L or by CD40 ligation through mab engagement with or without TLR triggering. In these culture systems we examined the effect of calcineurin inhibitors Tacrolimus and Cyclosporin, cell cycle blocking agents Mycophenolic acid (MPA) and Sirolimus and the anti-cd20 monoclonal antibody Rituximab on the proliferative capacity as well as IgG and IgM antibody production of B cells. Different results were obtained for the calcineurin inhibitors and the drugs that inhibit the cell cycle. Cyclosporin was moderately effective in inhibiting B cell proliferation, IgG and IgM production when B cells were triggered with CD40 ligation with or without TLR triggering. There was no effect of Cyclosporin on proliferation and antibody production when B cells were triggered by accessory cells. Tacrolimus failed to inhibit B cell responses in any of the culture systems. In contrast, MPA and Sirolimus were extremely potent in inhibiting B cell proliferation and antibody production, irrespective of the method of B cell triggering. In any of the culture systems used, the anti-cd20 humanized mab Rituximab had very limited effect or no effect. The observation of clearly distinct inhibitory patterns of these immunosuppressive drugs on B cell functionality has implications for the immunosuppressive regimens used in transplant patients undergoing rejection episodes. Funding This study was funded by the Landsteiner Foundation for Blood Transfusion Research and the Dutch Kidney Foundation, project number C00.6011 27

Successfull tapering of immunosuppression to low dose monotherapy steroids after living related HLA-identical renal transplantation J. van de Wetering, J. H. Gerrits, N. M. van Besouw, J. van Gestel, W. Weimar. Dept of Internal Medicine and Transplantation, Erasmus MC, University Hospital Rotterdam, Rotterdam, The Netherlands Introduction: Living related HLA-identical renal transplant (RTx) recipients often receive standard immunosuppression, despite the inherent complications of long-term immunosuppression. However, no data are available on the need for immunosuppression for these patients. We wondered whether their immunosuppressive load could be radical reduced. Method: Between November 1982 and November 2005, 83 living related HLAidentical RTx were performed in our center. Unadjusted graft survival was 74% at 10 years. Patients > 1 year after RTx, with stable renal function, without proteinuria and on triple or dual immunosuppression were enrolled in a one year tapering regime of immunosuppression to prednisone monotherapy 5 mg/day. Results: Twenty-nine patients were included. Median time after transplantation was 5.6 (range 1.0-21.4) years; median age was 51(range 21-66) years. Three (10%) of the 29 patients showed a recurrence of their original disease in their renal biopsy, after being on monotherapy prednisone for 1, 13 and 21 months respectively. Despite proteinuria, serum creatinine levels remained stable in 2 patients. One showed a transient rise in serum creatinine level, which stabilized after reintroduction of mycophenolate mofetil and raising the prednisone dose. Two additional patients showed a rise in serum creatinine levels. One of them had a chronic urinary tract infection. The other patient had a JC-virus urinary infection. She developed an untreatable vascular rejecttion after her immunosuppressive medication was reduced to prednisone 10 mg/day, combined with leflunomide 30 mg/day. In 24 (83%) of the 29 patients the immunosuppression could be successfully be reduced to prednisone monotherapy 5 mg/day. No significant changes in serum creatinine levels, 99 µmol/l (range 63-196) vs. 98 µmol/l (range 63-213), or protein excretion, 0.08 g/l (range 0.02-0.19) vs. 0.09 (range 0.04-0.66) were observed during 12 months of prednisone monotherapy. Conclusion: From this study we conclude that HLA-identical living related renal transplant recipients who are at least one year after transplantation might be treated with low dose steroid monotherapy. 28

Characterization of natural Tregs in non-human primates K. Haanstra, M. Jonker. Biomedical Primate Research Centre, Rijswijk, The Netherlands Regulatory T-cells are an important target of current research to develop protocols that induce tolerance towards an allograft. Many protocols that result in tolerance in mice do not result in tolerance in humans and non-human primates. It is therefore important to evaluate tolerance induction protocols in a relevant preclinical model. We have characterized rhesus monkey CD25+ cells phenotypically and functionally. CD4+CD25- and CD4+CD25+ T-cells were analyzed by FACS. Expression of the Treg markers CTLA-4 and FOXP3 is almost absent from CD4+CD25- cells, while they are expressed at high levels on CD25high cells. The CD25high population had increased expression of CD45RA and CD62L as compared to CD25int cells, indicating that CD25high cells contain more naive T-cells. Rhesus monkey CD4+CD25+ cells were separated from CD4+CD25- cells using the MACS system. CD25+ were in general unresponsive upon TCR-mediated signalling via plate-bound αcd3 and upon allogeneic stimulation. CD25- cells were stimulated with plate-bound αcd3, ConA and/or allogeneic stimulation. CD25+ cells were added to the cultures under varying experimental conditions. Proliferation of CD4+CD25- cells stimulated by αcd3 was inhibited when rhesus CD4+CD25+ were added in a 1:1 ratio to 31% of the proliferation of CD4+CD25- cells alone and proliferation of CD4+CD25- alloreactive cells was reduced to 56%. Human Tregs do not produce IL-2, IFN- γ and only little IL-10. The cytokine production of rhesus CD25+ cells stimulated with αcd3 was investigated. No IL-2 production was detected and IFN-γ and IL-10 production was very low. Furthermore, we determined that CD25+ cells can inhibit the IL-2 and IFN-γ production by CD25- cells, dose-dependently when decreasing numbers of CD4+CD25+ cells were added to αcd3 stimulated CD25- cells, whereby IL-2 production was more effectively inhibited than IFN-γ production. In addition we found that rhesus monkey CD25+ cells inhibit via a cell-cell contact dependent mechanism, as established in Transwell cultures and by addition of antibodies against IL-10 and TGF-γ. In conclusion, rhesus monkey CD4+CD25+ cells have similar phenotypic and functional characteristics as human Tregs. These findings allow testing of tolerance induction protocols via Treg expansion and/or induction in a relevant pre-clinical model. 29

Should the mycophenolate mofetil dose be based on total or unbound mycophenolic acid exposure when renal function is impaired or when albumin levels are low? R.M. van Hest 1, T. van Gelder 1,2, A.G. Vulto 1, L.M. Shaw 3 and R.A. Mathot 1. Depts of Clinical Pharmacology 1 and Internal Medicine 2, Erasmus MC, Univeristy Medical Center, Rotterdam, The Netherlands and Dept of Pathology & Laboratory Medicine 3, University of Pennsylvania, Philadelphia, USA Impaired renal function (RF) and low plasma albumin levels (ALBM) are significantly associated with decreased total exposure to mycophenolic acid (MPA). As hypothesis for the underlying mechanism it was proposed that low ALBM and accumulation of the glucuronide metabolite of MPA (MPAG), occurring during renal impairment, decrease the binding of MPA to albumin. The subsequent increase of MPA unbound fraction (f u = [unbound exposure] / [total exposure] * 100%) produces an increased total MPA clearance. The aim of this study was to elucidate the mechanism of the effect of RF and ALBM on total MPA exposure, as well as to assess whether unbound MPA exposure is affected. This knowledge helps to determine whether mycophenolate mofetil (MMF) dose adjustments are necessary when RF is impaired or when ALBM is low. Retrospective pharmacokinetic data of unbound and total MPA, and total MPAG were obtained from 88 renal transplant recipients. Data were available on day 11 and day 140 after transplantation. All patients were concurrently treated with cyclosporine and steroids. Data were analyzed using the non-linear mixed effects modeling program, NONMEM. The protein binding of MPA was significantly correlated with creatinine clearance (CrCl), ALBM and the MPAG concentration (p<0.001): a reduction of CrCl from 60 to 10 ml/min correlated with an increase of f u from 2.7% to 4.6%, accumulation of total MPAG concentrations from 50 to 150 mg/l correlated with an increase of f u from 2.8% to 3.7%, and a change in plasma albumin level from 40 to 30 g/l correlated with an increase of f u from 2.6% to 3.4%. No significant correlations were detected between the exposure to unbound MPA and ALBM, CrCl and MPAG concentration. The results support the hypothesis that low CrCl, low ALBM, and high MPAG concentrations decrease total MPA exposure through decreased MPA binding to albumin, as f u is significantly increased, while unbound MPA exposure is unaffected. The relationship between f u and MPAG concentrations suggests that MPAG displaces MPA from its albumin binding sites. Because unbound MPA is regarded as the pharmacologically active moiety, MMF dose adjustments may not be indicated when RF is impaired or when ALBM are low, even when total MPA concentrations are outside the therapeutic window. 30

Identification of 3 novel non-hla target Antigens recognized after Kidney Transplantation H.G. Otten 1, M. van Loon 1, W.G.J. van Ginkel 1, E.A. van de Graaf 2 and R.J. Hené 3. Depts of Immunology 1, Heart-Lung Center Utrecht 2 and Nephrology 3, University Medical Center, Utrecht, The Netherlands The presence of alloantibodies against HLA antigens before transplantation is associated with kidney graft rejection. Recently it was demonstrated that alloimmunization is associated with chronic graft loss in HLA-identical sibling kidney transplantation, indicating a role for immunity against non-hla antigens in rejection. However, the identity of these antigens recognized after alloimmunization is largely unknown. The main purpose of this study is to identify non-hla antigens recognized by antibodies from patients awaiting kidney retransplantation. To this end, 7 patients (M/F = 3/4; median age = 48; range = 29-60 years) were selected having rejected their kidney. Serum was taken after nephrectomy and analyzed for reactivity against an epithelial cell proteinexpression library by serological analysis of recombinant cdna expression libraries (SEREX). Recognized gene-products were identified after sequencing and analysis by the NCBI/BLAST server. From a total number of +2x10 5 geneproducts analysed, 3 different non-hla antigens were recognized by individual patient sera. Cross-sectional analysis indicated that these antigens - tetraspanin 8, LPLUNC1 and C20orf3 - were recognized by 4/7, 5/7 and 3/7 patient sera tested respectively, but not by sera from 2 healthy controls. In order to purify these antigens and enable large scale analysis of seroreactivity in different patient groups, the genes encoding tetraspanin 8 and C20orf3 have now been recloned in a pgex plasmid expression vector yielding the entire proteins as fusions with glutathione S-transferase. We conclude that antibodies directed against non-hla antigens are present after nephrectomy, and that their target antigens can be identified using the SEREX technique. Identification of these antigens will improve our comprehension of the pathogenesis of rejection, whereas antibody screening for several of these antigens may be used to improve donor selection. 31