Lack of evidence for a role of islet autoimmunity in the aetiology of canine diabetes mellitus

PLoS One. 2014 Aug 25;9(8):e105473. doi: 10.1371/journal.pone.0105473. eCollection 2014.

Abstract

Aims/hypothesis: 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/interpretations: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / metabolism
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / immunology
  • Diabetes Mellitus / veterinary*
  • Dog Diseases / blood
  • Dog Diseases / immunology*
  • Dogs
  • Fluorescent Antibody Technique
  • Humans
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / metabolism

Substances

  • Autoantibodies
  • islet cell antibody

Grant support

This work was supported by the European Commission (FP7-LUPA, GA-201370), the Swedish Research Council, the Torsten and Ragnar Söderberg Foundation, The NovoNordisk Foundation and Agria Djurförsäkringar Research Foundation. KLT is the recipient of EURYI award from the ESF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.