Evidence for Allograft Rejection in an Islet Transplant Recipient and Effect on β-Cell Secretory Capacity

Abstract

AbstractContext: The majority of islet transplant recipients experience a gradual decline in islet graft function, but the identification of islet-specific immune responses remains uncommon.Objectives: The aim was to present a case in which decline in islet graft function was accompanied by the appearance of islet donor-specific alloantibodies and demonstrate the effect on β-cell secretory capacity, an estimate of functional β-cell mass.Setting: The study was conducted at the Transplant Center and General Clinical Research Center of the University of Pennsylvania.Results: A 42-yr-old woman with type 1 diabetes who had a living-related kidney transplant received two intraportal islet infusions of a total 17,525 islet equivalents per kg body weight 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 U insulin daily. The decline in clinical islet graft function coincided with the detection of islet donor-specific human leukocyte antigen class I antibodies. β-Cell function and secretory capacity were assessed by the insulin secretory responses to iv glucose, arginine (AIRarg), and glucose-potentiated arginine (AIRpot) before and at alloantibody detection. The acute insulin response to glucose was almost entirely lost, whereas the AIRarg and AIRpot both decreased by approximately 50%.Conclusions: Because the AIRpot, a measure of β-cell secretory capacity, provides an estimate of functional β-cell mass, this case documents that islet graft loss can coincide with donor human leukocyte antigen sensitization and that the effect on β-cell mass may be best estimated from the AIRarg or AIRpot.