title: MHC class II risk haplotype associated with canine chronic superficial keratitis in German Shepherd dogs.
abstract: Canine chronic superficial keratitis (CSK) is an inflammatory ocular disease of an autoimmune origin leading to blindness if untreated. The main symptoms of CSK are progressive, bilateral vascularisation, fibrous tissue formation and pigmentation of the anterior corneal stroma. Although CSK is found in many breeds it is most prevalent in German Shepherd dogs (GSDs). Since Major Histocompatibility Complex (MHC) class II is associated with several autoimmune diseases in dogs we investigated the possible role of DLA-DRB1, -DQA1 and -DQB1 in GSDs affected with CSK. Our study population included 25 healthy controls and 30 CSK dogs. Most of the affected dogs were females suggesting a female predisposition. We identified 11 unevenly distributed haplotypes of which DLA-DRB1*01501/DQA1*00601/DQB1*00301 was significantly associated with the CSK dogs (OR=2.67, CI=1.17-6.44, p=0.02). We also found that overall homozygosity of MHC class II increases risk for CSK (OR=4.37, CI=1.27-18.46, p=0.02) and homozygosity of the risk haplotype by over eight-fold (OR=8.5, 95% CI=1.4-224, p=0.017). This study identifies a MHC class II risk haplotype for CSK in GSD and further supports the autoimmune origin of the disease.
authors.affiliation: Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Agnes Sjöbergin katu 2, P.O. Box 66, 00014 University of Helsinki, Finland. pzjokine@gmail.com
authors.forename: Päivi
authors.initials: P
authors.lastname: Jokinen
authors.forename: Elina M
authors.initials: EM
authors.lastname: Rusanen
authors.forename: Lorna J
authors.initials: LJ
authors.lastname: Kennedy
authors.forename: Hannes
authors.initials: H
authors.lastname: Lohi
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004283:Dog Diseases / Q000453:epidemiology / Q000235:genetics*; D004285:Dogs; D005260:Female; D005802:Genes, MHC Class II; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006720:Homozygote; D007634:Keratitis / Q000453:epidemiology / Q000235:genetics / Q000662:veterinary*; D008297:Male; D016017:Odds Ratio; D012306:Risk
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II