Pretransplant Donor-Specific Anti-Hla Antibodies Increase Severity Of Acute Cellular Rejection And Antibody Mediated Rejection After Intestinal Transplantation

Introduction: Long-term allograft loss remains a major obstacle to successful intestinal transplantation (ITx). There is increasing evidence that the presence of donor-specific antibodies (DSA) against human leukocyte antigens before ITx portend a worse outcome; our aim was to investigate the impact of DSA on ITx outcomes. Methods: We conducted a prospective longitudinal analysis of ITx to determine the incidence of DSA and association with Acute Cellular Rejection (ACR) and graft loss from 2007-2020. Recipients were managed in a protocolized manner with immunological testing, including complement dependent cytoxicity, panel reactive antibody, crossmatching (XM), and single antigen testing, at evaluation, wait-time, ITx, and post-ITx. Induction immunotherapy included interleukin-2 receptor antagonist (IL2RA) or rabbit anti-thymocyte globulin (ATG). Standard criteria for allograft monitoring were undertaken. Rejection was graded according to international standards. Study endpoints were: time/grade of first ACR, time/grade of worst ACR, and graft loss. Results: 68 primary ITx were undertaken including liver inclusive (n=44) and non-liver inclusive (n=24) ITx. The DSA+ group was older, received ATG induction, had a higher PRA, positive XM, and worse ACR.Conclusion: Pre-transplant DSA is a risk factor for severe ACR and graft loss despite the use of stronger induction immunotherapy. This study indicates the need to avoid ITx across DSA due to detrimental impact.