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Published on: March 10, 2021
MHC class II polymorphism is associated with a canine SLE-related disease complex
Maria Wilbe1, Päivi Jokinen, Christina Hermanrud
1Department of Animal Breeding and Genetics, BMC, Swedish University of Agricultural Sciences, Box 597, SE-751 24, Uppsala, Sweden. Maria.Wilbe@hgen.slu.se
Immunogenetics
|July 29, 2009
Summary
Nova Scotia duck tolling retrievers with immune-mediated rheumatic disease (IMRD) have a genetic risk associated with specific DLA class II genes. Homozygosity for a particular DLA II haplotype significantly increases IMRD risk, especially in ANA-positive cases.
Area of Science:
- Veterinary Genetics
- Immunology
- Canine Autoimmune Diseases
Background:
- Nova Scotia duck tolling retrievers are prone to immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA).
- IMRD symptoms include lameness, stiffness, and joint pain, often with antinuclear autoantibody (ANA) reactivity.
- SRMA presents as fever and neck stiffness in young dogs, treatable with corticosteroids.
Purpose of the Study:
- To investigate the role of Major Histocompatibility Complex (MHC) class II genes as a genetic risk factor for IMRD and SRMA in Nova Scotia duck tolling retrievers.
- To identify specific DLA class II alleles and haplotypes associated with disease susceptibility.
Main Methods:
- Sequence-based typing of DLA-DRB1, -DQA1, and -DQB1 class II loci was performed.
- Genotyping included 176 dogs: 51 IMRD cases (33 ANA-positive), 49 SRMA cases, and 78 healthy controls.
- Statistical analysis, including odds ratios (OR), was used to assess the association between DLA II genotypes and disease risk.
Main Results:
- Homozygosity for the DLA-DRB1*00601/DQA1*005011/DQB1*02001 haplotype significantly increased IMRD risk (OR=4.9), particularly for ANA-positive IMRD (OR=7.2).
- A general heterozygote advantage was observed; homozygotes had a higher risk (OR=4.4) compared to heterozygotes.
- The identified risk haplotype contains the RARAA amino acid epitope, a known shared epitope in human rheumatoid arthritis. No association was found for SRMA.
Conclusions:
- DLA class II genes are a significant genetic risk factor for ANA-positive IMRD in Nova Scotia duck tolling retrievers.
- The study identified a specific IMRD-associated risk haplotype within DLA II, with increased risk in homozygous dogs.
- Results suggest a narrow diversity of DLA II haplotypes in this breed, predisposing them to autoimmune diseases.
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