Correction: 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.

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.…”

Novel Locus Associated with Symmetrical Lupoid Onychodystrophy in the Bearded Collie

“…The condition was first described in 1992 by Scott and Miller [5], with most research since then focusing on diagnosis and treatment [2,3,6,7,8]. While disease etiology remains unclear, histopathological findings from nail biopsies and successful responses to immunosuppressive therapy have suggested an autoimmune component [4,9]. According to literature, SLO is considered rare in the general dog population, although German Shepherds [8], Gordon and English Setters [10], Giant Schnauzers and Bearded Collies [9] appear to be predisposed.…”

“…While disease etiology remains unclear, histopathological findings from nail biopsies and successful responses to immunosuppressive therapy have suggested an autoimmune component [4,9]. According to literature, SLO is considered rare in the general dog population, although German Shepherds [8], Gordon and English Setters [10], Giant Schnauzers and Bearded Collies [9] appear to be predisposed. A study that surveyed 104 randomly chosen Norwegian owners of Gordon and English Setters identified a 12.6% prevalence of the condition in those breeds [10].…”

“…Since certain breeds appear to be predisposed to SLO, the genetic components behind the condition have been investigated. In 2010, Wilbe et al identified a dog leukocyte antigen (DLA) class II risk haplotype associated with SLO in Gordon Setters, and suggested a similar association in Bearded Collies [9]. A genome-wide association study (GWAS) subsequently identified a region of association on canine chromosome (CFA) 12 (12:555,475-3,775,420) that includes the DLA class II genes in English and Gordon Setters [4].…”

“…Combined, these findings support an autoimmune etiology for SLO. However, similar to other autoimmune diseases, SLO appears to be inherited as a complex trait [4,9,13], requiring a combination of genetic and environmental factors. Despite a strong association, the DLA class II risk haplotypes fail to completely explain disease expression in the studied breeds [9,12].…”