title: 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.
authors.affiliation: Miami Transplant Institute, 1801 NW 9th Ave, Highland Professional Building, Miami, FL, 33136, USA. gburke@med.miami.edu.|Department of Surgery, Division of Transplantation, University of Miami Miller School of Medicine, Miami, FL, USA. gburke@med.miami.edu.
authors.forename: George W
authors.initials: GW
authors.lastname: Burke
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Vendrame
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Sahil K
authors.initials: SK
authors.lastname: Virdi
authors.affiliation: Miami Transplant Institute, 1801 NW 9th Ave, Highland Professional Building, Miami, FL, 33136, USA.|Department of Surgery, Division of Transplantation, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: G
authors.initials: G
authors.lastname: Ciancio
authors.affiliation: Miami Transplant Institute, 1801 NW 9th Ave, Highland Professional Building, Miami, FL, 33136, USA.|Department of Surgery, Division of Transplantation, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Chen
authors.affiliation: Miami Transplant Institute, 1801 NW 9th Ave, Highland Professional Building, Miami, FL, 33136, USA.|Department of Surgery, Division of Transplantation, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Ruiz
authors.affiliation: Department of Epidemiology and Public Health Sciences, Division of Biostatistics, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Shari
authors.initials: S
authors.lastname: Messinger
authors.affiliation: Benaroya Research Institute, Seattle, WA, USA.
authors.forename: Helena K
authors.initials: HK
authors.lastname: Reijonen
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.|Department of Medicine, Division of Endocrinology and Metabolism, University of Miami Miller School of Medicine, Miami, FL, USA.|Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pugliese
mesh_terms: D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015551:Autoimmunity; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000601:surgery; D006801:Humans; D010179:Pancreas / Q000276:immunology / Q000601:surgery; D016035:Pancreas Transplantation; D012008:Recurrence
chemical_list: D001323:Autoantibodies
keywords: Autoantibodies; Autoreactive T cells; Islet autoimmunity; Pancreas transplantation; Recurrent diabetes; Type 1 diabetes