Intestinal Transplantation in the Sensitized Transplant Recipient

Abstract

Introduction: Intestinal transplantation (ITx) recipients are frequently sensitized to donor antigen due to factors such as multiple bloodstream infections and repeated blood transfusions. Significant HLA sensitization has complicated post transplant immunological response and is considered prohibitive to ITx at many transplant centers. We report our experience with sensitized ITx recipients in both the adult and pediatric population. Methods: Retrospective analysis of all isolated ITx performed at our institution from November 2003 to December 2011. HLA antibody testing was done using a Luminex-based single antigen assay. Recipients were considered sensitized if PRA > 0%. Standard immunosuppression(IS) consisted of IL2 blockade induction with maintenance IS of tacrolimus, steroids and sirolimus. Sensitized(SZ) isolated ITx recipients received thymoglobulin induction and IVIg followed by standard maintenance IS. Intestinal biopsies were obtained on protocol. Standard grading was used for histological diagnosis of ACR. Results: 146 ITx were performed in 143 recipients. 91 cases were unsensitized(USZ) (PRA =0%) and 55 were sensitized. Donor and recipient characteristics were well matched between the USZ and SZ cases. In the USZ group(45 adult/46 peds), 40 (44%)cases were liver graft-inclusive, and in the SZ group (28 adult/27 peds), 22(40%) were liver-inclusive. Average PRA in the SZ group was 44.0 ± 34.6 %. 13 cases were highly sensitized, with PRA > 80%. 1 year Freedom from Rejection (FFR) was 71% in the USZ group, and 60% in the SZ group (p = ns). 3 year FFR was 66.3% in the USZ group, and 42.5% in the SZ group 9 (p = 0.06). In the USZ group 1 year FFR by graft type (Isolated, Liver-Intestine, Multivisceral) was 60.3%, 76.5%. 90.1% respectively. In the SZ group, 1 year FFR by graft type (Isolated, Liver-Intestine, Multivisceral) was 50.9%, 73.5%, 77.8% respectively. Comparing SX and USZ groups by graft type: Isolated ITx (p = ns); Liver-Intestine (p = ns); Multivisceral (p = ns). In the highly sensitized group (PRA> 80%), 1 year FFR was 52.7%. Compared to the USZ group (71%), this was not significantly different (p = 0.13) Conclusion: Intestinal transplantation in the SZ intestinal failure recipient can be performed with comparable short term immunological outcomes as the USZ recipient, even in the highly sensitized recipient. The identification of the SZ recipient preoperatively and the use of cellular depleting induction agents may contribute to this observation. Inclusion of a liver in the composite ITx graft appears to have an immunological benefit in both the SZ and USZ groups. Longer follow up is necessary to determine the long term immunologic sequela of sensitization in ITx.