Effect of Preformed Donor-Specific Antibodies in Intestine/Multivisceral Transplantation

Abstract

Aim: Donor specific antibodies have been postulated to precede rejection and have been associated with poor outcomes. We aimed to analyze the effect of preformed donor-specific antibodies (DSA) in intestine/multivisceral transplantation patients. Methods: Single-center retrospective review of preformed and de novo DSAs of all intestine/multivisceral transplant recipients was performed. Immunosuppression protocol included induction with anti-thymocyte globulin (r-ATG, 2 mg/kg on post-operative day [POD] 0, 2 and 4) and rituximab (150 mg/m2 on POD 1). Maintenance immunosuppression regimen included tacrolimus and prednisolone. Patients who had a positive crossmatch at transplant received 5 doses of r-ATG (10mg/kg in total) instead of the usual 3 doses. Patients who had developed de novo DSAs alone were excluded from the analysis. Patients categorized based on the absence (Group 1) and presence (Group 2) of preformed DSAs. Incidence of rejection and outcomes in terms of graft and patient survival were studied. Survival was analyzed using log rank test. Results: 23 patients underwent 26 intestinal/multivisceral transplantation between August 2010 and July 2016. Seventeen (65.4%) isolated intestinal, 7 (26.9%) multivisceral and 2 (7.7%) modified multivisceral transplants were performed. Of these, 14 cases belonged to Group 1 and 9 to Group 2. Three cases were excluded due to de novo DSAs alone. Eight (34.8%) cases had positive crossmatches at transplant. Group 2 had significantly higher positive crossmatches (77.8%) compared to Group 1 (7.1%) (p=0.001). The average panel-reactive antibody (PRA) at transplant was 39.0%. PRA was also significantly higher in group 2 with 82.3% compared to group 1 with 11.1% (p<0.001). Ten (43.5%) grafts developed acute rejection with 4 having recurrent episodes. In the Group 1, 7 (50%) cases developed graft rejections with 2 developing recurrent episodes compared to 3 (33.3%) cases of rejection with 2 developing recurrence in Group 2. Rejection rates were similar in both groups (p=0.67). Graft survival was also similar in both groups with median survival of 983 days in group 1 and 1300 days in group 2 (p=0.38). Conclusion: Preformed DSAs did not influence the occurrence of rejection or graft survival. While larger dose of r-ATG with rituximab induction might alleviate an impact of positive crossmatch, specific therapy may not be necessary only for positive preformed DSA if crossmatch is negative.