Evaluation for type 1 diabetes associated autoantibodies in diabetic and non-diabetic Australian terriers and Samoyeds

Allison L O’Kell,Mark A Atkinson,Clive H Wasserfall,Paula S Henthorn,Rebecka S Hess

doi:10.1186/s40575-020-00089-5

Abstract

BackgroundEvidence for an autoimmune etiology in canine diabetes is inconsistent and could vary based on breed. Previous studies demonstrated that small percentages of diabetic dogs possess autoantibodies to antigens known to be important in human type 1 diabetes, but most efforts involved analysis of a wide variety of breeds. The objective of this study was to evaluate the presence of glutamic acid decarboxylase 65 (GAD65), insulinoma-associated protein 2 (IA-2), and zinc transporter 8 (ZnT8) autoantibodies in diabetic and non-diabetic Australian Terriers and Samoyeds, two breeds with comparatively high prevalence of diabetes, in the United States.ResultsThere was no significant difference in the proportion of samples considered positive for GAD65 or ZnT8 autoantibodies in either breed evaluated, or for IA-2 autoantibodies in Australian Terriers (p > 0.05). The proportion of IA-2 autoantibody positive samples was significantly higher in diabetic versus non-diabetic Samoyeds (p = 0.003), but substantial overlap was present between diabetic and non-diabetic groups.ConclusionsThe present study does not support GAD65, IA-2, or ZnT8 autoantibodies as markers of autoimmunity in canine diabetes in Samoyeds or Australian Terriers as measured using human antigen sandwich enzyme-linked immunosorbent (ELISA) assays. Future studies using canine specific assays as well as investigation for alternative markers of autoimmunity in these and other canine breeds are warranted.

Highlights

Evidence for an autoimmune etiology in canine diabetes is inconsistent and could vary based on breed
Most dogs with diabetes have a deficiency in the production of insulin, a hormone produced by the pancreas that reduces blood sugar, due to a loss of the insulin producing cells in the pancreas (β-cells)
Canine diabetes is considered to be similar to human type 1 diabetes (T1D) [1]; some important unknowns persist with respect to the disease pathogenesis in dogs that are well established in the human form of the disease

Summary

Introduction

Evidence for an autoimmune etiology in canine diabetes is inconsistent and could vary based on breed. The objective of this study was to evaluate the presence of glutamic acid decarboxylase 65 (GAD65), insulinomaassociated protein 2 (IA-2), and zinc transporter 8 (ZnT8) autoantibodies in diabetic and non-diabetic Australian Terriers and Samoyeds, two breeds with comparatively high prevalence of diabetes, in the United States. Autoantibodies are well established biomarkers in T1D, especially those that target insulin, glutamic acid decarboxylase 65 (GAD65), insulinoma associated protein 2 (IA-2), and zinc transporter 8 (ZnT8) [3, 5]. Autoantibodies to IA-2 were observed in 10% of diabetic dogs using a canine specific assay [10] and 0% of diabetic dogs using a human assay [11]; the latter study found no diabetic or control dogs to be positive for ZnT8 autoantibodies using a human assay

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