Promoter-region alleles of the TNF-alpha and IL-10 genes have no effect on pretransplant alloantibody production.

BACKGROUND: The presence of high levels of alloantibodies are known to be a risk factor in renal graft outcome. Expression level polymorphisms in cytokine genes are also thought to have an effect on allograft outcome, but the studies examining this have been inconsistent. This may be due to center-specific differences in immunosuppressive protocols. Therefore, we studied the effects of these polymorphisms on pretransplant class I alloantibody production in nonexogenously immunosuppressed candidates. METHODS: Tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) gene polymorphisms were assayed genotypically by PCR-SSP on 177 renal transplant candidates. Candidates with a peak goat antihuman immunoglobulin-enhanced T-cell panel reactive antibody (PRA) of >or=10% were considered to be positive for alloantibody (32% of 177 total). RESULTS: Previous transplants, transfusions, or pregnancies were all associated with alloantibody production, but TNF-alpha and IL-10 phenotypes were not. High levels of alloantibody production (peak PRA >50%) were also not effected by cytokine phenotype. CONCLUSIONS: These data suggest that differences in TNF-alpha and IL-10 phenotype do not effect a patient's likelihood of becoming sensitized by transfusions, pregnancies, and prior transplants.

TNF-alpha, IL-6, IFN-gamma, and IL-10 gene expression polymorphisms and the IL-4 receptor alpha-chain variant Q576R: effects on renal allograft outcome.

BACKGROUND: There has been much interest recently in the effects of various cytokine gene expression polymorphisms on graft outcome. However, the results of these investigations reveal the outcomes to be organ-specific and center-specific. We sought to confirm and add to some of the earlier findings by studying the impact of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), interferon-gamma (IFN-gamma), and interleukin-6 (IL-6) polymorphisms and the interleukin-4 (IL-4) receptor alpha-chain variant on posttransplant renal allograft outcome. METHOD: TNF-alpha, IL-6, IFN-gamma, and IL-10 gene promoter region polymorphisms were assayed genotypically by PCR-SSP on 120 patients transplanted at the Albany Medical Center. These patients were also typed for the IL-4 receptor alpha-chain variant Q576R. RESULTS: Producers of high levels of the proinflammatory cytokine TNF-alpha were found to be at increased risk for acute rejection episodes if the allograft was mismatched for the molecular products of the class II region of the human major histocompatibility complex (HLA-DR). Expression level polymorphisms of the IL-6, IFN-gamma, and IL-10 genes were not associated with acute rejection episodes, nor was the IL-4 receptor alpha-chain variant Q576R. CONCLUSIONS: These data would suggest that the production of high levels of the cytokine TNF-alpha is especially detrimental to graft survival when the recipient's T-helper lymphocytes are being activated by mismatched donor HLA-class II antigens. Typing all potential kidney recipients for TNF-alpha, and providing well-matched organs for high producers of this cytokines, may be expected to increase rejection-free graft survival in these patients.