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Lessons From Pancreas Transplantation in Type 1 Diabetes: Recurrence of Islet Autoimmunity

Abstract

Type 1 diabetes recurrence (T1DR) affecting pancreas transplants was first reported in recipients of living-related pancreas grafts from twins or HLA identical siblings; given HLA identity, recipients received no or minimal immunosuppression. This observation provided critical evidence that type 1 diabetes (T1D) is an autoimmune disease. However, T1DR is traditionally considered very rare in immunosuppressed recipients of pancreas grafts from organ donors, representing the majority of recipients, and immunological graft failures are ascribed to chronic rejection. We have been performing simultaneous pancreas–kidney (SPK) transplants for over 25 years and find that 6–8 % of our recipients develop T1DR, with symptoms usually becoming manifest on extended follow-up. T1DR is typically characterized by (1) variable degree of insulitis and loss of insulin staining, on pancreas transplant biopsy (with most often absent), minimal to moderate and rarely severe pancreas, and/or kidney transplant rejection; (2) the conversion of T1D-associated autoantibodies (to the autoantigens GAD65, IA-2, and ZnT8), preceding hyperglycemia by a variable length of time; and (3) the presence of autoreactive T cells in the peripheral blood, pancreas transplant, and/or peripancreatic transplant lymph nodes. There is no therapeutic regimen that so far has controlled the progression of islet autoimmunity, even when additional immunosuppression was added to the ongoing chronic regimens; we hope that further studies and, in particular, in-depth analysis of pancreas transplant biopsies with recurrent diabetes will help identify more effective therapeutic approaches.

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Acknowledgments

Studies by the authors reviewed here were supported by grants from the National Institutes of Health (R01 DK070011, R01 DK052068), the JDRF (17-2011-594, 17-2012-3), the American Diabetes Association (RA-1-09-RA-413), the John C. Hench Foundation, and the Diabetes Research Institute Foundation, Hollywood, Florida. We are indebted to our research nurses, Lissett Tueros, Lois Hanson, and Sandra Flores.

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Correspondence to George W. Burke III.

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George W. Burke, III; Francesco Vendrame; Sahil K. Virdi; G. Ciancio; Linda Chen; Phillip Ruiz; Shari Messinger; Helena K. Reijonen; and Alberto Pugliese declare that they have no conflict of interest.

Ethical Approval

Studies described in this article involve human subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Our studies were approved by the University of Miami Institutional Review Board.

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Informed consent was obtained from all individuals who actively participated in the study. For some patients who did not actively participated in the study but whose data were retrospectively analyzed, studies were conducted under waiver of consent.

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For studies described that involved experimental animals, all applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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This article is part of the Topical Collection on Treatment of Type 1 Diabetes

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Burke, G.W., Vendrame, F., Virdi, S.K. et al. Lessons From Pancreas Transplantation in Type 1 Diabetes: Recurrence of Islet Autoimmunity. Curr Diab Rep 15, 121 (2015). https://doi.org/10.1007/s11892-015-0691-5

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Keywords

  • Type 1 diabetes
  • Pancreas transplantation
  • Recurrent diabetes
  • Islet autoimmunity
  • Autoantibodies
  • Autoreactive T cells