Association of an MHC Class II Haplotype with Increased Risk of Polymyositis in Hungarian Vizsla Dogs

Abstract

A breed-specific polymyositis is frequently observed in the Hungarian Vizsla. Beneficial clinical response to immunosuppressive therapies has been demonstrated which points to an immune-mediated aetiology. Canine inflammatory myopathies share clinical and histological similarities with the human immune-mediated myopathies. As MHC class II associations have been reported in the human conditions we investigated whether an MHC class II association was present in the canine myopathy seen in this breed. 212 Hungarian Vizsla pedigree dogs were stratified both on disease status and degree of relatedness to an affected dog. This generated a group of 29 cases and 183 “graded” controls: 93 unaffected dogs with a first degree affected relative, 44 unaffected dogs with a second degree affected relative, and 46 unaffected dogs with no known affected relatives. Eleven DLA class II haplotypes were identified, of which, DLA-DRB1*02001/DQA1*00401/DQB1*01303, was at significantly raised frequency in cases compared to controls (OR = 1.92, p = 0.032). When only control dogs with no family history of the disease were compared to cases, the association was further strengthened (OR = 4.08, p = 0.00011). Additionally, a single copy of the risk haplotype was sufficient to increase disease risk, with the risk substantially increasing for homozygotes. There was a trend of increasing frequency of this haplotype with degree of relatedness, indicating low disease penetrance. These findings support the hypothesis of an immune-mediated aetiology for this canine myopathy and give credibility to potentially using the Hungarian Vizsla as a genetic model for comparative studies with human myositis.

Associations between gastric dilatation-volvulus in Great Danes and specific alleles of the canine immune-system genes DLA88, DRB1, and TLR5

“…One reason for focusing on immune-related genes was the report 14 of co-occurrence of GDV with IBD, a disease with an etiology that clearly involves dysregulation of the immune system. Specific alleles or haplotypes of the DLA genes have been associated with several disorders in dogs, including exocrine pancreatic insufficiency, 72,78 hypoadrenocorticism, 79 diabetes mellitus, 73 polymyositis, 80 lymphocytic thyroiditis, 78 symmetrical lupoid onychodystrophy, 81 chronic superficial keratitis, 82 anal furunculosis, 83 and systemic lupus erythematosusrelated disease complex. 84 Similarly, mutations in TLR5 have been associated specifically with IBD in both dogs 63 and humans.…”

Systemic Acremonium species infection in a dog

“…Lymph nodes were not enlarged. Azotemia had further increased (creatinine 214 µmol/l, urea 15,20 mmol/l) and system, including MHC class II abnormalities (20), it can be speculated that this dog might have been particularly susceptible for fungal disease and dissemination. However, the exact source of exposure leading to the infection in this case could not be established.…”

Association ofDLA-DQB1alleles with exocrine pancreatic insufficiency in Pembroke Welsh Corgis

“…() or modified from Massey et al . () (Table S1). Products were purified according to Massey et al .…”

“…Products were purified according to Massey et al . () and sequenced on an ABI 3730xl Genetic Analyzer (Life Technologies). Results were compared with published nucleotide sequences to assign genotypes (Robinson et al .…”