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.
Bibliographical noteFunding Information:
This study was funded in part by a Morris Animal Foundation grant (#D12CA-031) to EF. Partial funding for EF was provided by an NIH ORIP K01 Mentored Research Scientist Development Award (1K01OD019912-01). JFM was supported in part by the Alvin S. and June Perlman Chair in Animal Oncology at the University of Minnesota. Donations to the Animal Cancer Care and Research Program of the University of Minnesota also helped support this project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
© 2016 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Copyright 2016 Elsevier B.V., All rights reserved.