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PLoS One. 2016 Mar 31;11(3):e0152397. doi: 10.1371/journal.pone.0152397. eCollection 2016.

Anti-Insulin Immune Responses Are Detectable in Dogs with Spontaneous Diabetes.

Kim JH1,2,3, Furrow E1, Ritt MG1, Utz PJ4,5, Robinson WH4,5, Yu L6, Eckert A7, Stuebner K2,7, O'Brien TD2,3,8,9, Steinman L5,10,11, Modiano JF1,2,3,9,12.

Author information

1
Department of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, St. Paul, MN, United States of America.
2
Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN, United States of America.
3
Masonic Cancer Center, University of Minnesota, Minneapolis, MN, United States of America.
4
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States of America.
5
Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, United States of America.
6
Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO, United States of America.
7
Clinical Investigation Center, University of Minnesota College of Veterinary Medicine, St. Paul, MN, United States of America.
8
Department of Veterinary Population Medicine, University of Minnesota College of Veterinary Medicine, St. Paul, MN, United States of America.
9
Stem Cell Institute, University of Minnesota, Minneapolis, MN, United States of America.
10
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States of America.
11
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, United States of America.
12
Center for Immunology, University of Minnesota, Minneapolis, MN, United States of America.

Abstract

Diabetes mellitus occurs spontaneously in dogs. Although canine diabetes shares many features with human type-1 diabetes, there are differences that have cast doubt on the immunologic origin of the canine disease. In this study, we examined whether peripheral immune responses directed against islet antigens were present in dogs with diabetes. Routine diagnostics were used to confirm diabetic status, and serum samples from dogs with (N = 15) and without (N = 15) diabetes were analyzed for the presence of antibodies against islet antigens (insulin, glutamic acid decarboxylase, insulinoma-associated protein tyrosine phosphatase, and islet beta-cell zinc cation efflux transporter) using standard radioassays. Interferon-γ production from peripheral blood T cells stimulated by porcine insulin and by human insulin was tested using Elispot assays. Anti-insulin antibodies were detectable in a subset of diabetic dogs receiving insulin therapy. Pre-activated T cells and incipient insulin-reactive T cells in response to porcine or human insulin were identified in non-diabetic dogs and in dogs with diabetes. The data show that humoral and cellular anti-insulin immune responses are detectable in dogs with diabetes. This in turn provides support for the potential to ethically use dogs with diabetes to study the therapeutic potential of antigen-specific tolerance.

PMID:
27031512
PMCID:
PMC4816536
DOI:
10.1371/journal.pone.0152397
[Indexed for MEDLINE]
Free PMC Article

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