Undine Gerlach¹, Constanze Schoenemann², Nils Lachmann², Peter Neuhaus¹, Andreas Pascher¹

¹Department for General, Visceral and Transplantation Surgery, Charite-Universitaetsmedizin, Berlin, Germany; ²Institute for Transfusion Medicine and Tissue Typing, Charite-Universitaetsmedizin, Berlin, Germany

Despite a negative crossmatch, intestinal transplant (ITX) recipients are capabale of mounting humoral immune reponses early after transplantation. The development of donorspecific HLA-antibodies (DSA) is associated with severe vascular graft injury and graft failure. We examined the development of HLA-antibodies in association with the clinical course and histopathological findings of 28 ITX recipients.

Between 06/2000 and 02/2011, 28 patients with a median age of 39.3  13.4 years received an isolated intestinal graft (n=18) or a multivisceral transplantation (n=10). HLA-antibodies were screened regularly before and after transplantation. Panel reactive antibodies (PRA) of >10% HLA I or II were considered positive. In case of DSA, treatment was initiated with plasmaphereses and ivIG. In the event of DSA-persistence and/or treatment refractory rejection, rituximab and/or bortezomib were added.

14 patients showed HLA-antibodies after transplantation. 5 developed non-donor-specific (NDSA) HLA-antibodies, whereas 9 showed strongly positive DSA (20%-82%) with significant rejection episodes around the time of positive samples. Interestingly, 8 patients showed DSA within 6 months after transplantation, whereas one patient developed DSA 10 years after ITX. All but one patient, who was successfully treated with steroid pulse therapy alone, received plasmapheresis and ivIG. Rituximab was added in 7 patients at a dose of 375 mg/m with 1.60.9 applications/patient. One patient developed a rituximab-resistant antibody-mediated rejection and was successfully treated with bortezomib. PRA-values decreased with antirejection-therapy in 8 of the 9 patients. One patient died of a severe therapy-refractory cellular and humoral rejection.

Development of HLA-antibodies after ITX is often significantly associated with acute rejection episodes. Early diagnosis and therapy is necessary to prevent severe graft injury and graft loss. Combination therapies including rituximab are mainly used to control rejection. However, proteasome inhibitors like bortezomib may serve as a new treatment option in cases of persistent DSA-levels and associated refractory rejection.