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Diabetes mellitus in dog -: No evidence for a type-1-like phenotype
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]


Diabetes mellitus (DM) is one of the most common endocrine disorders in dogs, and is commonly proposed to be of autoimmune origin. Although the clinical symptoms of human type 1 diabetes (T1D) and canine DM 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.


 Sera from 121 diabetic dogs representing 38 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs from 40 breeds. 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 immunoprecipitation.


None of the canine sera analyzed 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.


Based on sera from 121 diabetic dogs from 38 different breeds were tested for humoral autoreactivity using four different assays, contrary to previous observations, we find no support for an autoimmune aetiology  in canine diabetes.

Keyword [en]
Autoimmunity, autoantibodies, canine, diabetes mellitus, GAD65, ICA
National Category
Research subject
URN: urn:nbn:se:uu:diva-160539OAI: oai:DiVA.org:uu-160539DiVA: diva2:451294
Available from: 2011-10-25 Created: 2011-10-25 Last updated: 2011-11-23
In thesis
1. Immunological Studies using Human and Canine Model Disorders
Open this publication in new window or tab >>Immunological Studies using Human and Canine Model Disorders
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Immunologiska studier av modellsjukdomar i människa och hund
Abstract [en]

The studies presented in this thesis focus on human and canine models for autoimmune disease, with the main aim to gain new knowledge about disease mechanisms and to further evaluate the dog as a model for autoimmune disease.

Autoimmune Polyendocrine Syndrome type 1 (APS-1) is a hereditary human multiorgan disease caused by mutations in the autoimmune regulator (AIRE) gene. Hallmarks of APS-1 are chronic mucocutaneous candidiasis caused by Candida albicans, together with the autoimmune endocrine disorders hypoparathyroidism and adrenocortical failure. Many human diseases have an equivalent disease in dogs. Because humans share environment, and in part life style with the dogs they provide an interesting model for further genetic studies.

Immune responses to Candida albicans in APS-1 patients displayed an increased secretion of the proinflammatory cytokine IL-17A and similar results were also found in AIRE deficient mice. Anticytokine autoantibodies to IL-17A, IL-17F and IL-22 were detected in APS-1 patients, and a radioligand binding assay for measuring these autoantibodies was developed and evaluated.

In the canine studies we investigated whether canine diabetes mellitus could serve as a model for human autoimmune diabetes mellitus. Furthermore, we investigated type I IFN responses in Nova Scotia duck tolling retriever dogs with a systemic autoimmune disease resembling human SLE.

Four assays were used in search for signs of humoral autoimmunity in diabetic dogs. However, no evidence for a type 1 diabetes-like phenotype in dogs was found. Sera from Nova Scotia duck tolling retrievers suffering from steroid-responsive meningitis arteritis elicited an increased expression of IFN-inducible genes in the canine MDCK cell line. This suggests that these dogs have an IFN signature, as seen in human SLE.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 49 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 721
Autoimmunity, T cell, T helper cell, B cell, Autoantibodies, Interferon, Interleukin, Dogs, APS-1, Candida albicans, fungus
National Category
Basic Medicine
Research subject
Immunology; Medicine
urn:nbn:se:uu:diva-160550 (URN)978-91-554-8211-4 (ISBN)
Public defence
2011-12-08, Enghoffsalen, Akademiska sjukhuset. Ingång 50, bv, Uppsala, 09:15 (Swedish)
Available from: 2011-11-16 Created: 2011-10-25 Last updated: 2011-11-23Bibliographically approved

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Ahlgren, Kerstin. M
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