ASSOCIATION OF POLYMORPHISMS IN THE HUMAN INTERFERON -[gamma] AND INTERLEUKIN-10 GENE WITH ACUTE AND CHRONIC KIDNEY TRANSPLANT OUTCOME: The Cytokine Effect on Transplantation.
Asderakis, Argiris 1,2; Sankaran, David 3; Dyer, Phil 4; G. Johnson, Robert W. 1; Pravica, Vera 3; Sinnott, Paul J. 5; Roberts, Ian 1,4; Hutchinson, Ian V. 3
[Miscellaneous]
Transplantation.
71(5):674-678, March 15, 2001.
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Background. Our group has previously described five different size alleles of an interferon (IFN)-[gamma] microsatellite. Analyzing this polymorphism, this study correlated high IFN-[gamma] production with a 12 CA repeat allele (allele 2). Further, our group has described interleukin (IL)-10 polymorphism defining in vitro high and low IL-10 producer status.
Methods. Samples from 88 of 115 consecutive cadaveric renal transplants were used to define polymorphism of both IFN-[gamma] and IL-10. Patients were separated into high and low genotypes based on the previously reported association between certain genotypes and in vitro production. Graft survival, acute rejection, and serum creatinine at 5 years were analyzed for comparison between groups.
Results. The genotype associated with high IFN-[gamma] production was found in 70 patients. The incidence of acute rejection was 54.3% in the high IFN-[gamma] genotype group, compared with 44.4% in the low IFN-[gamma] group. Requirement for antithymocyte globulin therapy was greater in the high IFN-[gamma] group (odds ratio [OR]=2.5). Among HLA-DR-mismatched patients, IFN-[gamma] genotype was more strongly associated with rejection (OR=2.86). In the cyclosporine monotherapy subgroup, patients with high IFN-[gamma] genotype had a 61% incidence of rejection compared with only 20% in the low IFN-[gamma] genotype patients (OR=3.06). Graft survival was similar between the two groups. When 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 recipients at 5 years after transplantation (P =0.05). The high IL-10 genotype 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, particularly in patients on cyclosporine monotherapy. It is also associated with worse long-term graft function. On the contrary high IL-10 production may have a long-term protective effect.
(C) 2001 Lippincott Williams & Wilkins, Inc.
