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

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2008-06, Vol.23 (6), p.2016-2023
• Main Authors: Gerrits, Jeroen H., Wetering, Jacqueline van de, Drabbels, Jos J.M., Claas, Frans H.J., Weimar, Willem, Besouw, Nicole M. van
• Format: Article
• Language: English
• Subjects: Adult; alloreactivity; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Case-Control Studies; Cytokines - analysis; Cytokines - immunology; Elispot assay; Emergency and intensive care: renal failure. Dialysis management; Female; Graft Rejection; Graft Survival; Granzymes - immunology; Granzymes - metabolism; Histocompatibility Antigens - immunology; Histocompatibility Testing; HLA Antigens - analysis; Humans; IFN-γ; IL-10; Intensive care medicine; Interferon-gamma - analysis; Interferon-gamma - immunology; Interleukin-10 - analysis; Interleukin-10 - immunology; Interleukin-13 - analysis; Interleukin-13 - immunology; Isoantibodies - analysis; kidney transplantation; Kidney Transplantation - adverse effects; Kidney Transplantation - methods; Living Donors; Male; Medical sciences; Middle Aged; minor histocompatibility antigens; Monocytes - metabolism; non-HLA antigens; Probability; Reference Values; Risk Assessment; Sensitivity and Specificity; Statistics, Nonparametric; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; Transplantation Immunology - physiology
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfm899

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-γ-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-γ 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-γ 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-γ pc, IL-13 pc and GrB pc, suggests active downregulation of reactivity against non-HLA molecules.