BACKGROUNDAcute cellular rejection (ACR) is a common complication of small bowel transplantation (SBTx) and the major cause of graft loss. However, little is known regarding the genetic graft response to ACR in clinical transplants. In this study, we have determined a genetic expression profile of intestinal graft response to ACR after living related (LR) SBTx.RESULTSBy identifying the expression profiles of reported markers of rejection we were able to identify 57 genes that had significantly increased (more than twofold) expression in response to ACR. Known markers of rejection identified: MMP-9, MMP-2, VIP, IFNgamma, IL-2R, MADCAM-1, HSP-60, and HSP-70 all had greater than twofold increased expression after ACR diagnosed (week 3 to week 6). The newly identified genes were: IFI27, EPST11, APAF1, LAP3, STK6, and MDK.CONCLUSIONNewly identified up-regulated genes in response to ACR in small bowel graft are involved in the immune response, cell adhesion, neurogenesis, cell division and proliferation, DNA replication/repair, protein ubiquitin/proteolysis, and apoptosis. TNFalpha up-regulated early at week 2 biopsy may be an early genetic marker of ACR in SBTx.