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Doctoral thesis, 2018

Canine immune-mediated disease

Bremer, Hanna

Abstract

Immune-mediated diseases in dogs constitute a large group of disorders with the common attribute that they are caused by dysfunctions in the immune system. Broadly they can be classified into immunodeficiency disorders, allergies, and autoimmune diseases. Earlier studies have suggested that dogs of the breed Nova Scotia duck tolling retriever (NSDTR) are at increased risk of developing immune-mediated disorders. Two disorders have received particular attention: immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA). The major aims of this thesis were to 1) determine the incidence of immune-mediated disease in NSDTRs, 2) identify genetic risk factors for IMRD and SRMA, and 3) investigate the occurrence of different autoantibodies in dogs with autoimmune disease. Data from Agria Pet Insurance were used to estimate incidence of disease. Incidence of different immune-mediated diseases in NSDTRs was compared with that in other dog breeds. In general, the incidence for autoimmune diseases was three times higher in NSDTRs compared to other breeds. For IMRD and SRMA, the incidences were >10 times higher. Both IMRD and SRMA are complex genetic diseases and several genetic loci associated with the respective disease have been identified by our research group. We performed a detailed analysis of these loci and found 11 genes with altered gene expression associated with IMRD or SRMA. The majority of these genes were associated with either IMRD or with SRMA only, but one gene (AP3B2) showed association to both diseases. Autoantibodies are important hallmarks of autoimmune diseases, including IMRD. In the studies presented in this thesis, different methods were used to identify the autoantibody targets in dogs that were positive for antinuclear autoantibodies. Both previously reported and new canine autoantibodies were found. The interleukin enhancer-binding factors 2 and 3 (ILF2 and ILF3) appear to be common autoantibody targets in IMRD patients. These autoantibodies have not previously been described in dogs and have the potential to be used as diagnostic markers for canine systemic autoimmune disease.

Keywords

Antinuclear antibodies, autoimmunity, dog, gene expression, ILF2, ILF3, immune-mediated rheumatic disease, Nova Scotia duck tolling retriever, steroid-responsive meningitis-arteritis, systemic lupus erythematosus

Published in

Acta Universitatis Agriculturae Sueciae
2018, number: 2018:13
ISBN: 978-91-7760-166-1, eISBN: 978-91-7760-167-8
Publisher: Department of Clinical Sciences, Swedish University of Agricultural Sciences

Authors' information

Bremer, Hanna
Swedish University of Agricultural Sciences, Department of Clinical Sciences

UKÄ Subject classification

Clinical Science

URI (permanent link to this page)

https://res.slu.se/id/publ/104186