Long-term Persistence of Allosensitization After Islet Allograft Failure

Abstract

Background: Allosensitization has been reported after discontinuation of immunosuppression following graft failure in islet transplantation (ITx) recipients, though duration of its persistence is unknown.

Methods: We evaluated 35 patients with type 1 diabetes who received ITx, including 17 who developed graft failure (ITx alone, n = 13; ITx plus bone marrow-derived hematopoietic stem cells, n = 4) and 18 with persistent graft function. Panel-reactive antibody (PRA) was measured yearly for the duration of graft function within 1 y after graft failure at enrollment and yearly thereafter.

Results: In ITx alone graft failure patients, 61% (8/13) were PRA-positive at 6 y postgraft failure, and 46% (6/13) developed donor-specific anti-HLA antibodies (DSA to 2 ± 1 donors) during follow-up. The degree of sensitization was variable (cPRA ranging between 22% and 100% after graft failure). Allosensitization persisted for 7-15 y. Three subjects (3/13) were not allosensitized. In ITx plus bone marrow-derived hematopoietic stem cell recipients, cPRA-positivity (88%-98%) and DSA positivity persisted for 15 y in 75% (3/4) of subjects.

Conclusions: Allosensitization was minimal while subjects remained on immunosuppression, but after discontinuation of immunosuppressive therapy, the majority of subjects (77%) became allosensitized with persistence of PRA positivity for up to 15 y. Persistence of allosensitization in this patient population is of clinical importance as it may result in longer transplant waiting list times for identification of a suitable donor in the case of requiring a subsequent transplant.

Trial registration: ClinicalTrials.gov NCT02000687 NCT01999374 NCT01999361.