Abstract
Administration of insulin for treatment of diabetes mellitus in dogs can stimulate an immune response, with a proportion of animals developing anti-insulin antibodies (AIA). For an IgG antibody response to occur, this would require B cell presentation of insulin peptides by major histocompatibility complex (MHC) class II molecules, encoded by dog leukocyte antigen (DLA) genes, in order to receive T-cell help for class switching. DLA genes are highly polymorphic in the dog population and vary from breed to breed. The aim of the present study was to evaluate AIA reactivity in diabetic dogs of different breeds and to investigate whether DLA genes influence AIA status.Indirect ELISA was used to determine serological reactivity to insulin in diabetic dogs, treated with either a porcine or bovine insulin preparation. DLA haplotypes for diabetic dogs were determined by sequence-based typing of DLA-DRB1, -DQA1 and -DQB1 loci. Significantly greater insulin reactivity was seen in treated diabetic dogs (n=942) compared with non-diabetic dogs (n=100). Relatively few newly diagnosed diabetic dogs (3/109) were found to be AIA positive, although this provides evidence that insulin autoantibodies might be involved in the pathogenesis of the disease in some cases. Of the diabetic dogs treated with a bovine insulin preparation, 52.3% (182/348) were AIA positive, compared with 12.6% (75/594) of dogs treated with a porcine insulin preparation, suggesting that bovine insulin is more immunogenic. Breeds such as dachshund, Cairn terrier, miniature schnauzer and Tibetan terrier were more likely to develop AIA, whereas cocker spaniels were less likely to develop AIA, compared with crossbreed dogs. In diabetic dogs, DLA haplotype DRB1*0015--DQA1*006--DQB1*023 was associated with being AIA positive, whereas the haplotype DLA-DRB1*006--DQA1*005--DQB1*007 showed an association with being AIA negative. These research findings suggest that DLA genes influence AIA responses in treated diabetic dogs.
Highlights
Diabetes mellitus is one of the most common endocrine disorders in dogs, with an estimated prevalence of 0.32% in the UK (Davison et al, 2005)
Diabetic dogs treated with bovine insulin demonstrated significantly greater anti-insulin antibodies (AIA) reactivity than dogs treated with porcine insulin (P < 0.001)
In dogs treated with porcine insulin, 12% (75/594) were AIA positive, compared with 52% (182/348) of dogs treated with bovine insulin
Summary
Diabetes mellitus is one of the most common endocrine disorders in dogs, with an estimated prevalence of 0.32% in the UK (Davison et al, 2005). Certain breeds of dog are predisposed to developing diabetes, which strongly suggests that there is a genetic component to disease susceptibility (Catchpole et al, 2008). Breeds such as the Samoyed, Tibetan terrier and Cairn terrier have an increased risk of developing diabetes, whereas other breeds, such as the Boxer and German Shepherd Dog have a reduced risk (Catchpole et al, 2005). Three DLA haplotypes in particular, DLA-DRB1*009--DQA1*001--DQB1*008, DRB1*015--DQA1*006-DQB1*023 and DRB1*002--DQA1*009--DQB1*001, have been shown to be associated with susceptibility to diabetes and are prevalent in the Samoyed, Tibetan terrier and Cairn terrier breeds
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