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 polymorphism in cytokines might be important in the quality of allogeneic immune response. OBJECTIVES In this study HLA-DR matching and a number of cytokine gene polymorphisms have been evaluated in occurrence of acute rejection after living-unrelated donor (LURD) kidney transplantation. METHODS A total of 42 renal transplants that were performed at Hashemi Nejad Kidney Hospital (Tehran/Iran) and then followed up for 3 months post-transplantation were included in our study. Using PCR-SSP, HLA-DR alleles (DR1-18) of recipient and donor pairs and gene polymorphisms in TNF-, TGF-1, IL-10, IL-6, and IFN- of recipients were determined. RESULTS Acute rejection was observed in 11(26.2%) of 42 renal recipients. The frequency of one and two HLA-DR mismatches in rejector and nonrejector groups were 2(18.2%), 9(81.8%) and 13(41.9%), 17(54.8%) respectively. HLA-DR incompatibility was not significantly higher in rejector (1.820.40) than nonrejector (1.520.57) recipients (P=0.069) and more than half of nonrejectors had completely mismatched HLA-DR antigens with their donors. Polymorphisms associated with all the cytokines mentioned above were found to have no correlation with acute rejection. CONCLUSION Regarding to high frequency of HLA-DR mismatching in nonrejector group, we can postulate that the immunogenecity of LURD renal transplant is not similar to the cadaveric one, and predictive value of HLA-DR mismatching for acute rejection is not as reliable as in cadaveric transplant. Although, there is no doubt about influence of HLA compatibility on allograft survival. In addition, we failed to demonstrate further association between combined recipient cytokine genotypes and HLA-DR matching with acute rejection in this study. Thus, we conclude that a more detailed immunogenetic profile is necessary to predict transplant outcome or immunosuppression tailoring.