title: Lack of evidence for a role of islet autoimmunity in the aetiology of canine diabetes mellitus.
abstract: OBJECTIVE
  Diabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed to be of autoimmune origin. Although the clinical presentation of human type 1 diabetes (T1D) and canine diabetes are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported.
  
  
  METHODS
  Sera from 121 diabetic dogs representing 40 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immune precipitation. Sections of pancreata from five diabetic dogs and two control dogs were examined histopathologically including immunostaining for insulin, glucagon, somatostatin and pancreas polypeptide.
  
  
  RESULTS
  None of the canine sera analysed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Histopathology showed marked degenerative changes in endocrine islets, including vacuolisation and variable loss of immune-staining for insulin. No sign of inflammation was noted.
  
  
  CONCLUSIONS
  Contrary to previous observations, based on results from tests for humoral autoreactivity towards islet proteins using four different assays, and histopathological examinations, we do not find any support for an islet autoimmune aetiology in canine diabetes mellitus.
authors.affiliation: Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Kerstin M
authors.initials: KM
authors.lastname: Ahlgren
authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Tove
authors.initials: T
authors.lastname: Fall
authors.affiliation: Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Nils
authors.initials: N
authors.lastname: Landegren
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Grimelius
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: von Euler
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Sundberg
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America; Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lindblad-Toh
authors.affiliation: Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Lobell
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Åke
authors.initials: Å
authors.lastname: Hedhammar
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Andersson
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Helene
authors.initials: H
authors.lastname: Hansson-Hamlin
authors.affiliation: Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Åke
authors.initials: Å
authors.lastname: Lernmark
authors.affiliation: Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Kämpe
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000276:immunology / Q000662:veterinary*; D004283:Dog Diseases / Q000097:blood / Q000276:immunology*; D004285:Dogs; D005455:Fluorescent Antibody Technique; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; C024211:islet cell antibody