NDLI: MHC class II polymorphism is associated with a canine SLE-related disease complex

Content Provider	Springer Nature Link
Author	Wilbe, Maria Jokinen, Päivi Hermanrud, Christina Kennedy, Lorna J. Strandberg, Erling Hansson Hamlin, Helene Lohi, Hannes Andersson, Göran
Copyright Year	2009
Abstract	Nova Scotia duck tolling retrievers are predisposed to a SLE-related disease complex including immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis–arteritis (SRMA). IMRD involves symptoms that resemble those seen in systemic autoimmune rheumatic diseases, such as systemic lupus erythematosus, SLE, or SLE-related diseases, in humans. This disease complex involves persistent lameness, stiffness, mainly after resting, and palpable pain from several joints of extremities. The majority of affected dogs display antinuclear autoantibody (ANA)-reactivity. SRMA is manifested in young dogs with high fever and neck stiffness and can be treated with corticosteroids. We have investigated the possible role of MHC class II as a genetic risk factor in IMRD and SRMA etiology. We performed sequence-based typing of the DLA-DRB1, -DQA1, and -DQB1 class II loci in a total of 176 dogs including 51 IMRD (33 ANA-positive), 49 SRMA cases, and 78 healthy controls (two dogs were both IMRD- and SRMA-affected). Homozygosity for the risk haplotype DRB100601/DQA1005011/DQB1*02001 increased the risk for IMRD (OR = 4.9; ANA-positive IMRD: OR = 7.2) compared with all other genotypes. There was a general heterozygote advantage, homozygotes had OR = 4.4 (ANA-positive IMRD: OR = 8.9) compared with all heterozygotes. The risk haplotype contains the five amino acid epitope RARAA, known as the shared epitope for rheumatoid arthritis. No association was observed for SRMA. We conclude that DLA class II is a highly significant genetic risk factor for ANA-positive IMRD. The results indicate narrow diversity of DLA II haplotypes and identify an IMRD-related risk haplotype, which becomes highly significant in homozygous dogs.
Starting Page	557
Ending Page	564
Page Count	8
File Format	PDF
ISSN	00937711
Journal	Immunogenetics
Volume Number	61
Issue Number	8
e-ISSN	14321211
Language	English
Publisher	Springer-Verlag
Publisher Date	2009-07-28
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Canis familiaris MHC class II DLA Meningitis SLE Allergology Gene Function Cell Biology Human Genetics Immunology
Content Type	Text
Resource Type	Article
Subject	Genetics Immunology

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