2017 - CIRTA

1- Rejection of the Intestine Allograft

15.7 - Clinical significance of donor specific antibodies in the early course after intestinal transplantation

Presenter: Douglas, Farmer, Los Angeles, United States
Authors: Elaine Cheng, Robert Venick, Elizabeth Marcus, Marjorie-Anne Guerra, Suzanne McDiarmid, Douglas Farmer

Clinical significance of donor specific antibodies in the early course after intestinal transplantation

Elaine Y. Cheng1, Robert S. Venick2, Elizabeth A. Marcus2, Marjorie-Anne R. Guerra2, Suzanne V. McDiarmid2, Douglas G. Farmer1.

1Department of Surgery, University of California, Los Angeles, Los Angeles, CA, United States; 2Department of Pediatrics, University of California, Los Angeles, Los Angeles, CA, United States

Introduction: The impact of donor-specific anti-HLA antibodies (DSA) on patient and graft survival after intestinal transplantation (ITx) has yet to be completely elucidated. We prospectively monitored for DSA development with single-antigen bead Luminex testing per protocol prior to ITx, then post-tx at 1, 3, 6 months, and every 6 months thereafter.

Methods: Twenty-six ITx performed in 25 recipients between Jul 2011 and Aug 2016 were included in the study. Induction immunosuppression consisted of basiliximab for 6-8 weeks post-tx in normal-risk recipients and rATG/alemtuzumab in high-risk recipients (isolated intestinal transplants, presensitized patients and retransplants). Maintenance immunosuppression was tacrolimus-based with mycophenolate mofetil and prednisone in all cases. Median follow-up is 30.4 months.

Results: Of 26 transplants, 7 recipients (27%) harbored preformed DSA. Four of these recipients had persistent DSA after ITx, all of whom showed HLA class II antibodies. In 12 cases (46%) de novo DSA (dnDSA) emerged after transplant. Within this group, 10 recipients (83%) developed dnDSA in the early post-tx period (within 60 days). The presence of early dnDSA did not necessarily correlate with the clinical diagnosis of rejection (Fig.1). In contrast, in both patients who developed late dnDSA, the detection of antibodies was concurrent with acute rejection episodes. All patients with post-tx DSA were treated with augmented immunosuppression or antibody reduction therapy such as IVIG, rituximab, plasmapheresis, bortezomib and/or eculizumab. Only 3 recipients (25%) demonstrated persistent dnDSA, all of which were against class II antigens.

Acute rejection occurred in 7 patients (100%) who showed persistence of DSA post-tx, including 3 recipients who required allograft enterectomy (43%) due to complications from severe refractory rejection. In contrast, patients who cleared DSA experienced similar rejection rates to patients without DSA (57% vs. 50%), and no grafts were lost to rejection in either group.

Conclusions: De novo DSA is a common occurrence in the early course after ITx and can be detected in nearly one-half of recipients within the first 60 days. The emergence of early dnDSA does not correlate with clinical allograft dysfunction, and DSA can be eliminated in the majority of cases. Inferior outcomes with elevated risks of rejection and graft failure are only observed in the small subset of recipients with persistent DSA.

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