Preformed Donor Specific Antibody Increases The Risk of Severe Acute Rejection and Graft Loss in Isolated Intestine Transplant.

Abstract

Introduction: There is increasing evidence for donor specific antibody (DSA) as a risk factor for acute rejection following intestine transplantation. Methods: Beginning in 2008 all isolated intestine transplant recipients were prospectively evaluated for preformed DSA. HLA antibody testing was performed using a Luminex-based single-antigen assay. Strength and specificity were evaluated by antibody titer and median fluorescence intensity (MFI). Standard immunosuppression (IS) consisted of IL2 blockade induction with maintenance IS of tacrolimus, sirolimus, and prednisone. Sensitized recipients received thymoglobulin induction and IVIG followed by standard maintenance IS. Sensitized recipients also underwent virtual cross-matching to minimize preformed DSA to 0 or low titer (1:16). Intestinal biopsies were obtained on protocol or for cause. Standard grading was used for histological diagnosis of ACR. Results: There were 61 patients who underwent isolated intestine transplant with a mean follow up of 30.7 +/- 17.9 months. There were 10 patients with preformed DSA at median titer of 1:16 (MFI ˜3000). Patients with preformed DSA (n=10) were compared to patients without preformed DSA (n=51). Mean PRA and incidence of positive flow cytometry cross-match (FC-XM) were significantly higher in the preformed DSA group.Table: No Caption available.The 1-year risk of acute rejection (AR), severe (grade 3) rejection and graft loss (including death) from AR was significantly higher in patients with preformed DSA. Overall 3-year patient survival (PS) was lower but not statistically different from patients without DSA.Table: No Caption available.Conclusions: Despite immunosuppression intensification and a virtual cross match protocol, preformed DSA was significantly associated with acute rejection and graft loss following isolated intestine transplant.