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

Abstract

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. 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 beta-cell secretory capacity, an estimate of functional beta-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. Beta-cell function and secretory capacity were assessed by the insulin secretory responses to iv glucose, arginine (AIR(arg)), and glucose-potentiated arginine (AIR(pot)) before and at alloantibody detection. The acute insulin response to glucose was almost entirely lost, whereas the AIR(arg) and AIR(pot) both decreased by approximately 50%. CONCLUSIONS: Because the AIR(pot), a measure of beta-cell secretory capacity, provides an estimate of functional beta-cell mass, this case documents that islet graft loss can coincide with donor human leukocyte antigen sensitization and that the effect on beta-cell mass may be best estimated from the AIR(arg) or AIR(pot).