title: Anti-Insulin Immune Responses Are Detectable in Dogs with Spontaneous Diabetes.
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.
authors.affiliation: Department of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, St. Paul, MN, United States of America.|Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN, United States of America.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, United States of America.
authors.forename: Jong-Hyuk
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, St. Paul, MN, United States of America.
authors.forename: Eva
authors.initials: E
authors.lastname: Furrow
authors.affiliation: Department of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, St. Paul, MN, United States of America.
authors.forename: Michelle G
authors.initials: MG
authors.lastname: Ritt
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States of America.|Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, United States of America.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Utz
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States of America.|Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, United States of America.
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO, United States of America.
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.affiliation: Clinical Investigation Center, University of Minnesota College of Veterinary Medicine, St. Paul, MN, United States of America.
authors.forename: Andrea
authors.initials: A
authors.lastname: Eckert
authors.affiliation: Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN, United States of America.|Clinical Investigation Center, University of Minnesota College of Veterinary Medicine, St. Paul, MN, United States of America.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Stuebner
authors.affiliation: Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN, United States of America.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, United States of America.|Department of Veterinary Population Medicine, University of Minnesota College of Veterinary Medicine, St. Paul, MN, United States of America.|Stem Cell Institute, University of Minnesota, Minneapolis, MN, United States of America.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: O'Brien
authors.affiliation: Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, United States of America.|Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States of America.|Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, United States of America.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Steinman
authors.affiliation: Department of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, St. Paul, MN, United States of America.|Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN, United States of America.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, United States of America.|Stem Cell Institute, University of Minnesota, Minneapolis, MN, United States of America.|Center for Immunology, University of Minnesota, Minneapolis, MN, United States of America.
authors.forename: Jaime F
authors.initials: JF
authors.lastname: Modiano
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000473:pathology* / Q000662:veterinary; D004285:Dogs; D058501:Enzyme-Linked Immunospot Assay; D007328:Insulin / Q000276:immunology* / Q000627:therapeutic use; D007330:Insulin Antibodies / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis; D007515:Islets of Langerhans / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D007328:Insulin; D007330:Insulin Antibodies; D007371:Interferon-gamma