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NDT Advance Access originally published online on December 22, 2007
Nephrology Dialysis Transplantation 2008 23(6):2016-2023; doi:10.1093/ndt/gfm899
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org



Donor-reactive cytokine profiles after HLA-identical living-related kidney transplantation

Jeroen H. Gerrits1, Jacqueline van de Wetering1, Jos J.M. Drabbels2, Frans H.J. Claas2, Willem Weimar1 and Nicole M. van Besouw1

1 Department of Internal Medicine – Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam 2 Department of Immunohaematology and Blood transfusion, Leiden University Medical Center, Leiden, The Netherlands

Correspondence and offprint requests to: Jeroen H. Gerrits, Department of Internal Medicine – Transplantation, Room Ee-563a, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, NL-3000 CA, Rotterdam, The Netherlands. Tel: +31-10-703-4521; Fax: +31-10-704-4718; E-mail: j.gerrits{at}erasmusmc.nl



  Abstract

Background. After HLA-identical living-related (LR) kidney transplantation, only non-HLA antigen mismatches between donor and recipient may exist. We questioned whether donor-reactive responses against non-HLA antigens could be found after HLA-identical LR kidney transplantation, and wondered whether donor reactivity in the HLA-identical setting was different from the HLA-mismatched setting during immunological quiescence. Healthy individuals served as controls.

Methods. Elispot assays were performed to determine the number of alloreactive IFN-{gamma}-producing cells (pc), IL-10 pc, granzyme B (GrB) pc and IL-13 pc from peripheral blood mononuclear cells (PBMC) of HLA-identical, HLA-mismatched LR kidney transplant recipients and healthy individuals.

Results. The frequency of alloreactive IFN-{gamma} pc, IL-13 pc and GrB pc was higher in healthy individuals compared to both transplant patient groups. In the HLA-identical group, significantly higher numbers of donor-reactive IL-10 pc were found compared to their autologous control. These frequencies were also higher compared to the HLA-mismatched and healthy control group. The number of donor-reactive GrB pc was higher in the HLA-mismatched group than in the HLA-identical group. Donor-reactive IFN-{gamma} pc and IL-13 pc were comparable in both transplant groups.

Conclusions. In recipients of HLA-identical LR kidney transplant, high donor-reactive IL-10 pc, in combination with low donor-reactive IFN-{gamma} pc, IL-13 pc and GrB pc, suggests active downregulation of reactivity against non-HLA molecules.

Keywords: alloreactivity; Elispot assay; IFN-{gamma}; IL-10; kidney transplantation; minor histocompatibility antigens; non-HLA antigens

Received for publication: 10. 8.07
Accepted in revised form: 26.11.07


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