title: Donor-reactive cytokine profiles after HLA-identical living-related kidney transplantation.
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.
authors.affiliation: Department of Internal Medicine - Transplantation, Erasmus MC, University Medical Center Rotterdam, The Netherlands. j.gerrits@erasmusmc.nl
authors.forename: Jeroen H
authors.initials: JH
authors.lastname: Gerrits
authors.forename: Jacqueline
authors.initials: J
authors.lastname: van de Wetering
authors.forename: Jos J M
authors.initials: JJ
authors.lastname: Drabbels
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.forename: Nicole M
authors.initials: NM
authors.lastname: van Besouw
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000032:analysis* / Q000276:immunology; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D053804:Granzymes / Q000276:immunology / Q000378:metabolism; D006680:HLA Antigens / Q000032:analysis*; D006649:Histocompatibility Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D016753:Interleukin-10 / Q000032:analysis / Q000276:immunology; D018793:Interleukin-13 / Q000032:analysis / Q000276:immunology; D007518:Isoantibodies / Q000032:analysis*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D014181:Transplantation Immunology / Q000502:physiology*
chemical_list: D016207:Cytokines; D006680:HLA Antigens; D006649:Histocompatibility Antigens; D018793:Interleukin-13; D007518:Isoantibodies; D016753:Interleukin-10; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes