Allosensitization of islet allograft recipients

The immune monitoring of islet transplant recipients includes the assessment of panel reactive antibodies (PRA). A negative association of PRA+ with allogeneic solid organ graft survival has been recognized, but scattered data is available for islet transplantation.

We performed a retrospective analysis of PRA status in 66 patients with type 1 diabetes mellitus recipient of islet allografts between 1985 and 2006.

Pretransplant PRA+ was observed in 10 subjects in the old trials and associated with kidney transplantation and/or pregnancies. Thirteen subjects displayed PRA+ at follow-up, eight of whom were de novo. Overall, PRA+ did not correlate with islet graft outcome: long-term graft survival was observed in the presence of basal or persistent PRA+ and graft dysfunction occurred also in the absence of PRA+. Loss of graft function was associated with PRA+ after lowering of immunosuppression or after infection episodes. Loss of C-peptide did not affect kidney graft function even in simultaneous islet-kidney transplant recipients. Mostly, PRA remained negative under adequate immunosuppression. Patients whose immunosuppression was discontinued invariably developed PRA+.

Monitoring of PRA under immunosuppression may have little clinical value under adequate immunosuppression in islet transplant recipients. The implications of allosensitization after discontinuation of immunosuppression need to be evaluated to define the real clinical impact in this patient population.