Keynote Message

Immune-mediated destruction of endocrine tissue is likely to be involved in the pathogenesis of several canine endocrinopathies, leading to hormone deficiency. Such immune-mediated endocrine diseases are relatively common in dogs and human beings, although there are some differences in terms of the evidence and nature of the autoimmune response. There seem to be some common immunogenetic factors associated with autoimmunity, some of which are likely to be involved in determining breed susceptibility. In hypothyroidism (lymphocytic thyroiditis), thyroid peroxidase is a major autoantigen in humans, although in dogs, thyroglobulin seems to be the major target. In hypoadrenocorticism (Addison's disease) autoantibodies directed against 21 hydroxylase predominate in humans, but the evidence for similar autoantibodies in dogs is conflicting, and there is evidence for P450 side-chain cleavage enzyme and 3 beta hydroxysteroid dehydrogenase as autoantigens. Canine diabetes mellitus has a more complex and heterogeneous pathogenesis, with primary immune-mediated destruction of pancreatic beta cells likely present in only a subpopulation of dogs, with autoantibodies against insulin and the 65 kDa isoform of glutamic acid decarboxylase (GAD65) demonstrated in some cases. Several genetic studies in different canine endocrinopathies have shown associations with immune-response genes, including dog leukocyte antigen (DLA), cytotoxic T lymphocyte antigen 4 (CTLA4) and various cytokines, although the specific variants involved might differ from breed to breed and other (non immunological) genetic factors are also likely to contribute. In this session, a comparative approach will be taken to focus on canine endocrinopathies in terms of the underlying immunopathogenesis, the genetic factors that are likely to be important, and the evidence for autoantibody and cell-mediated immune responses against endocrine tissue antigens.

Key References

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2.  Skopek E, Patzl M, Nachreiner RF. Detection of autoantibodies against thyroid peroxidase in serum samples of hypothyroid dogs. American Journal of Veterinary Research. 2006;67:809–814.

3.  Bianchi M, Dahlgren S, Massey J, et al. A multi-breed genome-wide association analysis for canine hypothyroidism identifies a shared major risk locus on CFA12. PLoS One. 2015;10:e0134720. DOI: 10.1371/journal.pone.0134720.

4.  Boag AM, Christie MR, McLaughlin KA, Syme HM, Graham P, Catchpole B. Autoantibodies against cytochrome P450 side-chain cleavage enzyme in dogs (Canis lupus familiaris) affected with hypoadrenocorticism (Addison's disease). PLoS One. 2015;10:e0143458. DOI: 10.1371/journal.pone.0143458.

5.  Boag AM, Catchpole B. A review of the genetics of hypoadrenocorticism. Topics in Companion Animal Medicine. 2014;29:96–101. DOI: 10.1053/j.tcam.2015.01.001.

6.  Holder AL, Kennedy LJ, Ollier WE, Catchpole B. Breed differences in development of anti-insulin antibodies in diabetic dogs and investigation of the role of dog leukocyte antigen (DLA) genes. Veterinary Immunology and Immunopathology. 2015;167:130–138. DOI: 10.1016/j.vetimm.2015.07.014.