Abstract
P1166 Aims: Despite advances in immunosupression therapy and post transplant management immunological pathways play an essential role in renal allograft dysfunctions (ischemia-reperfusion injury, acute rejection, chronic rejection). Alloantigen–dependent and alloantigen-independent immune processes, both are mediated by cytokines and chemokines. In recent decade cytokines, chemokines and their receptors have been shown to be highly polymorphic. The cytokines and chemokines gene polymorphisms are associated with cytokines, chemokines production, activity or ligand-receptor affinity. Many different polymorphisms were followed in transplant recipients with different and contradictory results. The aim of our study was to analyze the relation between selected cytokines and chemokines genes polymorphisms in kidney donors, recipients, donor-recipient match and post transplant outcome (incidence of rejection, 5 year graft function). Methods: Polymorphism of TGF-β, TNF-α, IL-6, IL-10, MCP-1, RANTES, CD-14 were determined using DNA PCR technology for 268 healthy volunteers (standard population sample), 345 kidney transplant recipients (transplanted from 1997 till 1999) and 298 their cadaveric donors. Patients were followed-up for 4-6 years (median 62months), serum creatinine, creatinine clearance were monitored. 12 months protocol biopsy was performed in 45,7% recipients. All significant graft dysfunctions were proved by core biopsy. 55 patients with long-term good and stable graft function (over 15 years) were also included into presented study. Results: Distribution of alleles of followed genes for cytokines and chemokines were identical in population sample, cadaveric donors as far as kidney transplant recipients. CD-14 gene polymorphism in donor, recipient and donor-recipient match had no impact on posttransplant outcome. Low TGF-β production genotype was associated with risk for recurrent rejection in first 6 months after transplantation. 4years graft function was significantly deteriorated in renal allograft recipients with low producing genotype. Only few patients with low TGF-β production genotype were found among recipients with long-functioning (over 15 years) graft. Only tendency for worse graft outcome (combined increase number of rejections, increase serum creatinine) was found in donor-recipients mismatch in TGF-β genotype (high producing kidneys transplanted into low producing recipients). Genetical determination for TNF-α and Il-10 production was associated with delayed graft function and rejection. Il-6 gene polymorphism had no impact on incidence of acute rejections in first six months after transplantation, but worse 5 years outcome of renal allograft was found. The MCP-1 and RANTES gene polymorphism had only partial effect on 4y graft outcome (tendency to deterioration in high producing genotypes) Conclusions: Our data support the hypothesis that the strength of alloimmune responsiveness after transplantation in part is genetically determined. The donor-recipient match in cytokine gene polymorphism has a marginal effect.
Published Version
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