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

Departments of Medicine, Division of Endocrinology, Diabetes, and Metabolism (M.R.R.), Pathology and Laboratory Medicine (M.K., J.K.), and Surgery, Division of Transplantation (J.F.M., A.N.), University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6149

Address all correspondence and requests for reprints to: Michael R. Rickels, M.D., University of Pennsylvania School of Medicine, Division of Endocrinology, Diabetes, and Metabolism, 778 Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104-6149. E-mail: rickels{at}mail.med.upenn.edu.

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 ß-cell secretory capacity, an estimate of functional ß-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. ß-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 ß-cell secretory capacity, provides an estimate of functional ß-cell mass, this case documents that islet graft loss can coincide with donor human leukocyte antigen sensitization and that the effect on ß-cell mass may be best estimated from the AIR_arg or AIR_pot.

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