Genetic expression profile during acute cellular rejection in clinical intestinal transplantation

Small bowel transplantation is a successful treatment for irreversible intestinal failure. Acute cellular rejection (ACR) represents the major cause of graft loss. However, little is known regarding the mechanisms of ACR and no data exist on the genetic response occurring during ACR. We report a genetic expression profile determined using oligo-microarrays of the intestinal graft during an ACR episode. Mucosal biopsies were obtained from the graft at weeks 0, 1, 2, 3, 6, and 52 posttransplant. We observed a statistically significant increase in transcript levels from 51 genes between biopsy samples from before ACR compared with during ACR. Functional analysis of these genes revealed an interferon (IFN)-alpha signature associated with a type I IFN immune response from dendritic cells or association with cellular proliferation and division. These genetic data support that dendritic cell activation was ongoing during ACR and suggest that IFNalpha production as a potential immunosuppressive target for transplantation.