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J Clin Endocrinol Metab. 2007 Jul;92(7):2410-4. Epub 2007 May 8.

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

Author information

  • 1Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6149, USA. rickels@mail.med.upenn.edu

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).

PMID:
17488791
[PubMed - indexed for MEDLINE]
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