The influence of selected cytokine gene polymorphisms on the occurrence of acute and chronic rejection and on kidney graft survival

摘要

Genetically determined interindividual differences in the production of mediators of immune response may influence the outcomes of kidney transplantation. Of the cytokine gene polymorphisms that determine the level of gene expression, TNF-α –308G/A, IFN-γ +874T/A and microsatellite (CA)_n, TGF-β₁ +869T/C and +915G/C, IL-6 –174G/C, and IL-10 –592C/A, –819C/T, and –1082G/A seem to have the strongest impact on graft survival. Increased risk of acute rejection (AR) was demonstrated for high-producing genotypes of pro-inflammatory cytokines such as TNF-α and IFN-γ, while the association with polymorphisms of TGF-β₁ and IL-10 remains unclear. A high production of profibrotic TGF-β1 is associated with interstitial fibrosis and tubular atrophy (IF/TA). In contrast, high genetically determined IL-6 gene expression played a protective role in the development of chronic rejection (CR). The risk of graft loss was greater among high TNF-α and low TGF-β₁ or IL-6 producers. The results of kidney transplantation are also influenced by the donor’s cytokine expression profile. Low IL-6 production donor genotype was associated with a higher prevalence of AR, CR, and IF/TA. Low donor transcriptional TGF-β₁ gene activity predisposed the recipient to AR episodes and high IFN-γ expression to IF/TA development. To date, study results are highly inconsistent, so the applicability of cytokine polymorphism genotyping remains questionable. In summary, it is difficult to conclude whether or not cytokine polymorphism genotyping is useful in the risk assessment of rejection and kidney graft survival and in applying optimal immunosuppressive medication.