Breed differences in development of anti-insulin antibodies in diabetic dogs and investigation of the role of dog leukocyte antigen (DLA) genes

Holder, Angela; Kennedy, L. J.; Ollier, William; Catchpole, Briän

doi:10.1016/j.vetimm.2015.07.014

Cited by 25 publications

(37 citation statements)

References 27 publications

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“…This may be analogous to humans who are positive for ICA yet negative for the other autoantibodies (63). Insulin autoantibodies have been detected in 3 of 109 (3%) (64) and 5 of 40 (12.5%) (65) untreated diabetic dogs. Proinsulin autoantibodies were found in 8 of 15 (53%) untreated and 6 of 15 (37.5%) insulin-treated diabetic dogs, but also in 3 of 15 (20%) of control dogs (66).…”

Section: Immunopathogenesismentioning

confidence: 99%

Comparative Pathogenesis of Autoimmune Diabetes in Humans, NOD Mice, and Canines: Has a Valuable Animal Model of Type 1 Diabetes Been Overlooked?

et al. 2017

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Despite decades of research in humans and mouse models of disease, substantial gaps remain in our understanding of pathogenic mechanisms underlying the development of type 1 diabetes. Furthermore, translation of therapies from preclinical efforts capable of delaying or halting β-cell destruction has been limited. Hence, a pressing need exists to identify alternative animal models that reflect human disease. Canine insulin deficiency diabetes is, in some cases, considered to follow autoimmune pathogenesis, similar to NOD mice and humans, characterized by hyperglycemia requiring lifelong exogenous insulin therapy. Also similar to human type 1 diabetes, the canonical canine disorder appears to be increasing in prevalence. Whereas islet architecture in rodents is distinctly different from humans, canine pancreatic endocrine cell distribution is more similar. Differences in breed susceptibility alongside associations with MHC and other canine immune response genes parallel that of different ethnic groups within the human population, a potential benefit over NOD mice. The impact of environment on disease development also favors canine over rodent models. Herein, we consider the potential for canine diabetes to provide valuable insights for human type 1 diabetes in terms of pancreatic histopathology, impairment of β-cell function and mass, islet inflammation (i.e., insulitis), and autoantibodies specific for β-cell antigens.

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Section: Immunopathogenesismentioning

confidence: 99%

Comparative Pathogenesis of Autoimmune Diabetes in Humans, NOD Mice, and Canines: Has a Valuable Animal Model of Type 1 Diabetes Been Overlooked?

et al. 2017

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“…, Holder et al . ). Autoantibodies against other islet antigens have also been detected, though infrequently, in diabetic dogs (Davison et al .…”

Section: Introductionmentioning

confidence: 97%

“…) and patient‐specific factors (such as breed) may play a role in anti‐insulin antibody development (Holder et al . ). While the amino acid sequences of canine and porcine insulin are identical, bovine insulin differs from canine insulin by two amino acids and human insulin differs from canine insulin by one amino acid (Smith , Asadi et al .…”

Section: Introductionmentioning

confidence: 97%

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Exploratory analysis of anti‐insulin antibodies in diabetic dogs receiving recombinant human insulin

Lester

O'Kell

2020

J of Small Animal Practice

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Objectives To quantify anti‐insulin antibodies in diabetic dogs treated with recombinant human insulin and to determine if insulin dosage or duration of treatment differed between anti‐insulin antibody‐positive and ‐negative diabetic dogs. Materials and Methods Descriptive preliminary study using serum from 24 client‐owned diabetic dogs treated for a minimum of 2 weeks with recombinant human insulin, and 24 client‐owned healthy control dogs without diabetes. Sera were analysed by radioimmunoassay for anti‐insulin antibodies. The proportion of antibody positive dogs was compared between groups by Fisher's exact test. Results Four diabetic (16.6%) and no control dogs were anti‐insulin antibody positive. Clinical Significance These results indicate that treatment with recombinant human insulin may induce anti‐insulin antibodies in dogs, although this finding needs to be re‐investigated in a larger study to investigate the impact of anti‐insulin antibodies on glycaemic control.

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“…Although these studies reinforce the impression of important homology between dog and human immunobiology, especially in cancer, they also highlight the correlative nature of many canine studies with a notable absence of carefully controlled and functional experiments to satisfy high levels of evidence regarding causation and mechanism. Interestingly, there is evidence for breed effects on immune function which likely relate to the inheritance of particular haplotypes of major histocompatibility complex (MHC) genes and further reinforce the paradox that dogs are a highly outbred species which nevertheless manifest significant effects of genetic inbreeding [77–79]. …”

Section: Introductionmentioning

confidence: 99%

Canine cancer immunotherapy studies: linking mouse and human

Park¹,

Withers²,

Modiano³

et al. 2016

j. immunotherapy cancer

100

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Despite recent major clinical breakthroughs in human cancer immunotherapy including the use of checkpoint inhibitors and engineered T cells, important challenges remain, including determining the sub-populations of patients who will respond and who will experience at times significant toxicities. Although advances in cancer immunotherapy depend on preclinical testing, the majority of in-vivo testing currently relies on genetically identical inbred mouse models which, while offering critical insights regarding efficacy and mechanism of action, also vastly underrepresent the heterogeneity and complex interplay of human immune cells and cancers. Additionally, laboratory mice uncommonly develop spontaneous tumors, are housed under specific-pathogen free conditions which markedly impacts immune development, and incompletely model key aspects of the tumor/immune microenvironment. The canine model represents a powerful tool in cancer immunotherapy research as an important link between murine models and human clinical studies. Dogs represent an attractive outbred combination of companion animals that experience spontaneous cancer development in the setting of an intact immune system. This allows for study of complex immune interactions during the course of treatment while also directly addressing long-term efficacy and toxicity of cancer immunotherapies. However, immune dissection requires access to robust and validated immune assays and reagents as well as appropriate numbers for statistical evaluation. Canine studies will need further optimization of these important mechanistic tools for this model to fulfill its promise as a model for immunotherapy. This review aims to discuss the canine model in the context of existing preclinical cancer immunotherapy models to evaluate both its advantages and limitations, as well as highlighting its growth as a powerful tool in the burgeoning field of both human and veterinary immunotherapy.

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Breed differences in development of anti-insulin antibodies in diabetic dogs and investigation of the role of dog leukocyte antigen (DLA) genes

Cited by 25 publications

References 27 publications

Comparative Pathogenesis of Autoimmune Diabetes in Humans, NOD Mice, and Canines: Has a Valuable Animal Model of Type 1 Diabetes Been Overlooked?

Comparative Pathogenesis of Autoimmune Diabetes in Humans, NOD Mice, and Canines: Has a Valuable Animal Model of Type 1 Diabetes Been Overlooked?

Exploratory analysis of anti‐insulin antibodies in diabetic dogs receiving recombinant human insulin

Canine cancer immunotherapy studies: linking mouse and human

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