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

Nephrol Dial Transplant. 2008 Jun;23(6):2016-23. doi: 10.1093/ndt/gfm899. Epub 2007 Dec 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cytokines / analysis*
  • Cytokines / immunology
  • Female
  • Graft Rejection
  • Graft Survival
  • Granzymes / immunology
  • Granzymes / metabolism
  • HLA Antigens / analysis*
  • Histocompatibility Antigens / immunology
  • Histocompatibility Testing
  • Humans
  • Interferon-gamma / analysis
  • Interferon-gamma / immunology
  • Interleukin-10 / analysis
  • Interleukin-10 / immunology
  • Interleukin-13 / analysis
  • Interleukin-13 / immunology
  • Isoantibodies / analysis*
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / methods*
  • Living Donors*
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Probability
  • Reference Values
  • Risk Assessment
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • Transplantation Immunology / physiology*

Substances

  • Cytokines
  • HLA Antigens
  • Histocompatibility Antigens
  • Interleukin-13
  • Isoantibodies
  • Interleukin-10
  • Interferon-gamma
  • GZMB protein, human
  • Granzymes