Lessons From Pancreas Transplantation in Type 1 Diabetes

Recurrence of Islet Autoimmunity

George W Burke, Francesco Vendrame, Sahil K. Virdi, Gaetano Ciancio, Linda J Chen, Phillip Ruiz, Shari Messinger, Helena K. Reijonen, Alberto Pugliese

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Article number121
Pages (from-to)1-9
Number of pages9
JournalCurrent Diabetes Reports
Volume15
Issue number12
DOIs
StatePublished - Dec 1 2015

Fingerprint

Pancreas Transplantation
Autoimmunity
Type 1 Diabetes Mellitus
Pancreas
Transplants
Recurrence
Immunosuppression
Biopsy
Graft Rejection
Hyperglycemia
Autoantibodies
Autoimmune Diseases
Siblings
Lymph Nodes
Tissue Donors
Insulin
Staining and Labeling
T-Lymphocytes
Kidney

Keywords

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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Lessons From Pancreas Transplantation in Type 1 Diabetes : Recurrence of Islet Autoimmunity. / Burke, George W; Vendrame, Francesco; Virdi, Sahil K.; Ciancio, Gaetano; Chen, Linda J; Ruiz, Phillip; Messinger, Shari; Reijonen, Helena K.; Pugliese, Alberto.

In: Current Diabetes Reports, Vol. 15, No. 12, 121, 01.12.2015, p. 1-9.

Research output: Contribution to journalArticle

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