title: Characterization of human organ donors testing positive for type 1 diabetes-associated autoantibodies.
abstract: In this study we aim to describe the characteristics of non-diabetic organ donors with circulating diabetes-associated autoantibodies collected within the Nordic Network for Islet Transplantation. One thousand and thirty organ donors have been screened in Uppsala for antibodies against glutamic acid decarboxylase (GADA) and islet antigen-2 (IA-2A). The 32 non-diabetic donors that tested positive for GADA (3.3% of all non-diabetic donors) were studied in more detail, together with 32 matched controls. Mean age among the autoantibody-positive donors was 52.6 (range 21-74), family history of type 1 diabetes (T1D) was unknown, and no donor was genetically predisposed for T1D regarding the human leucocyte antigen (HLA) locus. Subjects were analysed for islet cell antibodies (ICA), insulin autoantibodies (IAA) and zinc transporter 8 antibodies (ZnT8A), and pancreas morphology and clinical data were examined. Eight non-diabetic donors tested positive for two antibodies and one donor tested positive for four antibodies. No insulitis or other signs of a diabetic process were found in any of the donors. While inflammatory cells were present in all donors, subjects with high GADA titres had significantly higher CD45 cell numbers in exocrine tissue than controls. The extent of fibrosis was more pronounced in autoantibody-positive donors, even in subjects with lower GADA titres. Notably, it is possible that events not related directly to T1D (e.g. subclinical pancreatitis) may induce autoantibodies in some cases.
authors: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors: A
authors: A
authors: Wiberg
authors: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors: A
authors: A
authors: Granstam
authors: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors: S
authors: S
authors: Ingvast
authors: Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.|Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland.
authors: T
authors: T
authors: Härkönen
authors: Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.|Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland.|Folkkhälsan Research Center, Helsinki Finland.|Department of Pediatrics, Tampere University Hospital, Tampere, Finland.
authors: M
authors: M
authors: Knip
authors: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors: O
authors: O
authors: Korsgren
authors: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors: O
authors: O
authors: Skog
mesh_terms: D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology / Q000601:surgery; D046148:Donor Selection / Q000379:methods*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D016381:Islets of Langerhans Transplantation; D008297:Male; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology; D014019:Tissue Donors
chemical_list: D001323:Autoantibodies; C096322:ICA512 autoantibody; C516862:PTPRN protein, human; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase
keywords: autoantibodies; exocrine pancreas; fibrosis; inflammation; type 1 diabetes