Abstract

BACKGROUND: A growing body of evidence demonstrated an immune etiology as well as nonimmune mechanisms for episodes of clinical acute rejection and long-term allograft dysfunction. OBJECTIVE: To investigate the correlation of IFN-gamma-producing cells and TGF-beta with incidence of clinical acute rejection in living-related and unrelated kidney allogarft recipients during the first post-transplant year. METHODS: This multi-center study was performed on 57 kidney allograft recipients from living-related (n=20) and unrelated (n=37) donors between April 2011 and September 2012 and who were followed prospectively for a mean period of one year. Peripheral blood samples were collected from all patients pre-transplantation and at days 14, 30 and 90 after transplantation; PBMCs were used as responding cells in enzyme-linked immunosorbent spot (ELISPOT) assay to measure the frequency of IFN-gamma-producing cells after stimulation with donor lymphocytes. Additionally, TGF-beta levels were measured in cell culture supernatants of ELISPOT assay. RESULTS: During the follow-up period, 45 (79) patients were diagnosed with stable graft function (group A); 12 (21) experienced clinical acute rejection episodes (group B). The frequency of IFN-gamma-producing cells was significantly (p<0.001) higher in the rejection group in all three times after transplantation. Also, post-transplantation comparison for TGF-beta showed a significantly (p<0.001) higher contents in group A vs. group B. Comparing the post-transplantation levels of TGF-beta and mean numbers of IFN-gamma- producing cells between groups A and B demonstrated a continuous increment in TGF-beta and decreasing frequencies of IFN-gamma-producing cells in group A vs. group B. CONCLUSION: Serial post-transplantation monitoring of IFN-gamma-producing donor reactive cells during the first months is a clinically feasible approach for identification of kidney allogarft recipients at risk for ongoing immune-mediated graft damage and later graft loss.