Association of polymorphisms in the human interferon-gamma and interleukin-10 gene with acute and chronic kidney transplant outcome - The cytokine effect on transplantation

Background, Our group has previously described five different size alleles of an interferon (IFN)-gamma microsatellite, Analyzing this polymorphism, t his study correlated high IFN-gamma production with a 12 CA repeat allele ( allele 2), Further, our group has described interleukin (IL)-10 polymorphis m defining in vitro high and low IL-IO producer status, Methods. Samples from 88 of 115 consecutive cadaveric renal transplants wer e used to define polymorphism of both IFN-gamma and IL-10, Patients were se parated into high and low genotypes based on the previously reported associ ation between certain genotypes and in vitro production. Graft survival, ac ute rejection, and serum creatinine at B years were analyzed for comparison between groups. Results. The genotype associated with high IFN-gamma production was found i n 70 patients. The incidence of acute rejection was 54.3% in the high IFN-g amma genotype group, compared with 44.4% in the low IFN-gamma group. Requir ement for antithymocyte globulin therapy was greater in the high IFN-gamma group (odds ratio [OR]=2.5), Among HLA-DR-mismatched patients, IFN-gamma ge notype was more strongly associated with rejection (OR=2.86), In the cyclos porine monotherapy subgroup, patients with high IFN-gamma genotype had a 61 % incidence of rejection compared with only 20% in the low IFN-gamma genoty pe patients (OR=3.06), Graft survival was similar between the two groups. W hen the analysis was controlled for the presence of delayed graft function, 40.5% of the high IFN-gamma genotype patients had serum creatinine levels above 200 mu mol/L compared with only 14.3% of the low IFN-gamma genotype r ecipients at 5 years after transplantation (P=0.05), The high IL-10 genotyp e was shown to be associated with better graft function at 5 years (75 vs. 50%, P=0.09), Conclusion. In this study we have shown that high producer genotype for IFN -gamma may have an influence on acute rejection of kidney transplants, part icularly in patients on cyclosporine monotherapy, It is also associated wit h worse long-term graft function. On the contrary high IL-10 production may have a long-term protective effect.