Evidence for a genetic predisposition towards acute rejection after kidneyand simultaneous kidney-pancreas transplantation

Background. In vitro production of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin 10 (IL-10), and transforming gro wth factor-beta (TGF-beta) correlate with their respective genetic polymorp hisms. We analyzed the relationship between these genetic polymorphisms and posttransplant outcome. Methods. Using DNA polymerase chain reaction (PCR) technology, polymorphism s for TNF-alpha, IFN-gamma, IL-10, and TGF-beta were determined for 82 kidn ey (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-alpha production phenotype correlated with recurrent ac ute rejection (AR) episodes (P<0.026). Compared with the low TNF-alpha prod uction phenotype, more patients with the high production phenotype had a po st-AR serum creatinine >2.0 mg/dl, but this was not statistically significa nt (64 vs. 35%, P=0.12). There was no relationship between TNF-alpha genoty pe and the time to first AR episode or incidence of graft loss. IFN-gamma p roduction phenotype showed no correlation with any of these clinical outcom e parameters. There was an increase in AR incidence as the IL-10 production phenotype increased (low, intermediate, high), but only in low TNF-alpha p roducer phenotypes (P=0.023). Conclusions. Patients with a polymorphic cytokine genotype putatively encod ing for high in vivo TNF-alpha production, and to a lesser extent IL-10 cyt okine genotypes putatively encoding for higher levels of in vivo IL-10 prod uction, had a worse clinical outcome regarding AR episodes. These data supp ort the hypothesis that the strength of alloimmune responsiveness after tra nsplantation in part is genetically determined.