The Predictive Value of HLA-DR Matching and Cytokine Gene Polymorphisms in Renal Allograft Acute Rejection: A Living-unrelated Donor (LURD) Study

Background: In addition to Human Leukocyte Antigens (HLA) compatibility, gene polymorphisms in cytokines might also be important in the quality of allogeneic immune response. Objective: To evaluate the influence of HLA-DR matching and a number of cytokine gene polymorphisms on acute rejection after living-unrelated donor (LURD) kidney transplantation. Methods: A total of 42 renal transplants performed at Hashemi Nejad Kidney Hospital (Tehran/Iran) and followed up for 3 months post-transplantation were included. Using PCR-SSP, HLA-DR alleles (DR1- 18) of recipients and donors and gene polymorphisms in TNF-a, TGF-b1, IL-10, IL- 6, and IFN-g of recipients were determined. Results: Acute rejection was observed in 11(26.2%) of renal recipients. The frequency of one and two HLA-DR mismatches in rejector group was 2(18.2%) and 9(81.8%) and in non-rejector group was 13(41.9%) and 17(54.8%), respectively. HLA-DR incompatibility was not significantly higher in rejector (1.82 0.40) compared with non-rejector (1.52 0.57) recipients (P=0.069) and more than half of non-rejectors had completely mismatched HLA-DR antigens with donors. Polymorphisms associated with the mentioned cytokines had no correlation with acute rejection. Conclusion: The predictive value of HLA-DR mismatching for acute rejection is not as prominent in LURD kidney transplantation as in the cadaveric one. In addition, we failed to demonstrate an association between combined cytokine genotypes and HLA-DR matching with acute rejection. Further and more detailed immunogenetic investigations are required in order to have a better prediction of the transplant outcome.