Context: The majority of islet transplant recipients experience a gradual decline in islet graft function, but the identification of islet specific immune responses remains uncommon.

Objective: To present a case where decline in islet graft function was accompanied by the appearance of islet donor-specific alloantibodies and demonstrate the effect on -cell secretory capacity, an estimate of functional -cell mass.

Setting: The Transplant Center and General Clinical Research Center of the University of Pennsylvania.

Results: A 42 year-old woman with type 1 diabetes who had a living-related kidney transplant received two intraportal islet infusions of a total 17,525 IEs/kg under daclizumab, prednisone, tacrolimus and rapamycin immunosuppression. She became insulin-independent, but 4 months later the rapamycin was discontinued for associated colitis. She remained normoglycemic for another 6 months before manifesting impaired fasting glucose and requiring 5 - 10 units of insulin daily. The decline in clinical islet graft function coincided with the detection of islet donor-specific anti-HLA Class I antibodies. -cell function and secretory capacity were assessed by the insulin secretory responses to intravenous glucose (AIR_glu), arginine (AIR_arg), and glucose-potentiated arginine (AIR_pot) before and at the time of alloantibody detection. The AIR_glu was almost entirely lost while the AIR_arg and AIR_pot both decreased by 50%.

Conclusions: Because the AIR_pot, a measure of -cell secretory capacity, provides an estimate of functional -cell mass, this case documents that islet graft loss can coincide with donor HLA sensitization and that the effect on -cell mass may be best estimated from the AIR_arg or AIR_pot.