Evidence for allograft rejection in an islet transplant recipient and effect on beta-cell secretory capacity.
BACKGROUND
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
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.


METHODS
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).
Rickels
Michael R
MR
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6149, USA. rickels@mail.med.upenn.edu
Kamoun
Malek
M
Kearns
Jane
J
Markmann
James F
JF
Naji
Ali
A
D000328:Adult; D000918:Antibody Specificity; D001120:Arginine; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D005260:Female; D005947:Glucose; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism; D006680:HLA Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D011183:Postoperative Complications; D014019:Tissue Donors; D014184:Transplantation, Homologous
D006680:HLA Antigens; D001120:Arginine; D005947:Glucose