Long-term Persistence of Allosensitization After Islet Allograft Failure.

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 year after graft failure at enrollment and yearly thereafter.

RESULTS: In ITx alone graft failure patients, 61% (8/13) were PRA-positive at 6 years 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 to 15 years. Three subjects (3/13) were not allosensitized. In ITx plus bone marrow-derived hematopoietic stem cell recipients, cPRA-positivity (88% to 98%) and DSA-positivity persisted for 15 years 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 years. 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 case of requiring a subsequent transplant.