DLA Class II Alleles Are Associated with Risk for Canine Symmetrical Lupoid Onychodystropy (SLO)

Abstract

Symmetrical lupoid onychodystrophy (SLO) is an immune-mediated disease in dogs affecting the claws with a suggested autoimmune aethiology. Sequence-based genotyping of the polymorphic exon 2 from DLA-DRB1, -DQA1, and -DQB1 class II loci were performed in a total of 98 SLO Gordon setter cases and 98 healthy controls. A risk haplotype (DRB1*01801/DQA1*00101/DQB1*00802) was present in 53% of cases and 34% of controls and conferred an elevated risk of developing SLO with an odds ratio (OR) of 2.1. When dogs homozygous for the risk haplotype were compared to all dogs not carrying the haplotype the OR was 5.4. However, a stronger protective haplotype (DRB1*02001/DQA1*00401/DQB1*01303, OR = 0.03, 1/OR = 33) was present in 16.8% of controls, but only in a single case (0.5%). The effect of the protective haplotype was clearly stronger than the risk haplotype, since 11.2% of the controls were heterozygous for the risk and protective haplotypes, whereas this combination was absent from cases. When the dogs with the protective haplotype were excluded, an OR of 2.5 was obtained when dogs homozygous for the risk haplotype were compared to those heterozygous for the risk haplotype, suggesting a co-dominant effect of the risk haplotype. In smaller sample sizes of the bearded collie and giant schnauzer breeds we found the same or similar haplotypes, sharing the same DQA1 allele, over-represented among the cases suggesting that the risk is associated primarily with DLA-DQ. We obtained conclusive results that DLA class II is significantly associated with risk of developing SLO in Gordon setters, thus supporting that SLO is an immune-mediated disease. Further studies of SLO in dogs may provide important insight into immune privilege of the nail apparatus and also knowledge about a number of inflammatory disorders of the nail apparatus like lichen planus, psoriasis, alopecia areata and onycholysis.

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

“…However, Wilbe et al [16] found the haplotype to be protective against the immune-mediated condition of Symmetrical Lupoid Onychodystrophy (SLO) in Gordon Setters.…”

A genome‐wide association study identifies a region strongly associated with symmetrical onychomadesis on chromosome 12 in dogs

“…The aim was to obtain DLA‐DRB1 , ‐ DQA1 and ‐ DQB1 exon 2 DNA sequences from all dogs; thus, 40 GS and 34 ES were genotyped in the present study, whereas 175 of the GS had been genotyped previously (Wilbe et al . ). DLA‐DRB1/DQA1/DQB1 haplotypes could not be determined for all dogs due to the fact that the DNA had been used up for the GWAS.…”

“…Methods for genotyping and classification of DNA sequences followed previously described methods (Wilbe et al . ), with the exceptions that DNA was extracted using an E.Z.N.A ® blood DNA kit (Omega Bio‐Tek), and the PCR products were sequenced on a 3500xL Genetic Analyzer (Applied Biosystems).…”

“…Like many other autoimmune diseases in humans and in dogs, associations of SO with the major histocompatibility complex [MHC; dog leukocyte antigen (DLA) in dogs] class II alleles have been revealed (Wilbe et al . ). However, previous studies of a few autoimmune diseases indicate that some of the reported DLA associations may be spurious and not causative (Safra et al .…”

Pathology in Practice

“…1,3 Symmetric lupoid onychodystrophy is an uncommon disease of the claw bed. [4][5][6] Some authors believe that the histopathologic changes associated with symmetric lupoid onychodystrophy are a reaction pattern rather than a separate disease entity. 4 Young to middle-aged adult dogs are affected by this syndrome.…”