EVIDENCE FOR A GENETIC PREDISPOSITION TOWARDS ACUTE REJECTION AFTER KIDNEY AND SIMULTANEOUS KIDNEY-PANCREAS TRANSPLANTATION1

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Abstract
In vitro production of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin 10 (IL-10), and transforming growth factor-β (TGF-β) correlate with their respective genetic polymorphisms. We analyzed the relationship between these genetic polymorphisms and posttransplant outcome. Using DNA polymerase chain reaction (PCR) technology, polymorphisms for TNF- α, IFN-γ, IL-10, and TGF-β 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. A high TNF-α production phenotype correlated with recurrent acute rejection (AR) episodes (P 2.0 mg/dl, but this was not statistically significant (64 vs. 35%, P =0.12). There was no relationship between TNF-α genotype and the time to first AR episode or incidence of graft loss. IFN-γ 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-α producer phenotypes (P =0.023). Patients with a polymorphic cytokine genotype putatively encoding for high in vivo TNF-α 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.