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Background. In vitro production of tumor necrosis factor-a (TNF-a), interferon-g (IFN-g), interleukin 10 (IL-10), and transforming growth factor-b (TGF-b) correlate with their respective genetic polymorphisms. We analyzed the relationship between these genetic polymorphisms and posttransplant outcome. Methods. Using DNA polymerase chain reaction (PCR) technology, polymorphisms for TNF- a, IFN-g, IL-10, and TGF-b were determined for 82 kidney (K) and 19 simultaneous kidney-pancreas (SKP) recipients. These results were analyzed with regard to the incidence of acute rejection (AR), and the timing and severity of the first AR episode. Results. A high TNF-a production phenotype correlated with recurrent acute rejection (AR) episodes (P 2.0 mg/dl, but this was not statistically significant (64 vs. 35%, P50.12). There was no relationship between TNF-a genotype and the time to first AR episode or incidence of graft loss. IFN-g production phenotype showed no correlation with any of these clinical outcome parameters. There was an increase in AR incidence as the IL-10 production phenotype increased (low, intermediate, high), but only in low TNF-a producer phenotypes (P50.023). Conclusions. Patients with a polymorphic cytokine genotype putatively encoding for high in vivo TNF-a production, and to a lesser extent IL-10 cytokine genotypes putatively encoding for higher levels of in vivo IL-10 production, had a worse clinical outcome regarding AR episodes. These data support the hypothesis that the strength of alloimmune responsiveness after transplantation in part is genetically determined. Acute rejection (AR) of solid organ transplants is the clinical manifestation of an uncontrolled alloimmune response directed against an engrafted organ. Lymphocyte stimulation by donor antigens derived from the allograft and pre |
