Department of Animal Breeding and Genetics, Biomedical Centre, Swedish University of Agricultural Sciences SLU, Uppsala, Sweden.
PLoS One. 2010 Aug 23;5(8):e12332. doi: 10.1371/journal.pone.0012332.
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 (DRB101801/DQA100101/DQB100802) 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 (DRB102001/DQA100401/DQB101303, 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.
对称性狼疮样甲营养不良症 (SLO) 是一种影响犬爪的免疫介导性疾病,其发病机制可能与自身免疫有关。本研究对 98 例 SLO 戈登猎犬病例和 98 例健康对照进行了多态性外显子 2 的基于序列的基因分型,该外显子位于 DLA-DRB1、-DQA1 和 -DQB1 类 II 基因座。在 53%的病例和 34%的对照组中存在风险单倍型(DRB101801/DQA100101/DQB100802),其发生 SLO 的风险比(OR)为 2.1。当比较携带风险单倍型的纯合子与不携带该单倍型的所有狗时,OR 为 5.4。然而,在 16.8%的对照组中存在一个更强的保护单倍型(DRB102001/DQA100401/DQB101303,OR=0.03,1/OR=33),但仅在 1 例(0.5%)中存在。保护单倍型的作用显然强于风险单倍型,因为 11.2%的对照组是风险和保护单倍型的杂合子,而这种组合在病例中不存在。当排除携带保护单倍型的狗时,与携带风险单倍型的杂合子相比,携带风险单倍型的纯合子的 OR 为 2.5,这表明风险单倍型存在共显性效应。在较小样本量的伯德梗和巨型雪纳瑞品种中,我们发现了相同或相似的单倍型,它们共享相同的 DQA1 等位基因,在病例中过度表达,这表明风险主要与 DLA-DQ 相关。我们得出了明确的结论,即 DLA Ⅱ类与戈登猎犬 SLO 发病风险显著相关,这支持 SLO 是一种免疫介导性疾病。对犬 SLO 的进一步研究可能为指甲器官的免疫特权以及扁平苔藓、银屑病、斑秃和甲分离等指甲器官的许多炎症性疾病提供重要的见解。