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法国斗牛犬和迷你短毛腊肠犬慢性肠炎相关的犬白细胞抗原(DLA)Ⅱ类基因型。

Dog leukocyte antigen (DLA) class II genotypes associated with chronic enteropathy in French bulldogs and miniature dachshunds.

机构信息

Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan.

Faculty of Veterinary Medicine, Okayama University of Science, 1-3 Ikoino-oka, Imabari, Ehime, 794-8555, Japan.

出版信息

Vet Immunol Immunopathol. 2021 Jul;237:110271. doi: 10.1016/j.vetimm.2021.110271. Epub 2021 May 23.

Abstract

Canine chronic enteropathy (CE) is a group of immunogenetic disorders of unclear etiology characterized by chronic or recurrent gastrointestinal signs and inflammation. Diagnosis of CE subtypes by treatment response is a lengthy and challenging process, particularly in refractory cases of the disease. Given known association of dog leukocyte antigen (DLA) class II genotype and various immunogenetic disorders between and across breeds, this study was designed to examine the potential of determining susceptibility to refractory CE through identification of risk and protective genotypes in French bulldogs and miniature dachshunds-two popular dog breeds in Japan. Sequence-based genotyping of three DLA class II genes in 29 French bulldogs and 30 miniature dachshunds with refractory CE revealed a protective haplotype DLA-DRB1002:01-DQA1009:01-DQB1001:01 against CE in French bulldogs (OR 0.09, 95 % CI 0.01-0.71, p = 0.0084). No statistical difference was noted between miniature dachshund cases and controls. These findings, largely disparate from a previous study on German shepherd dogs in the UK, were taken as possible indication of etiological differences in the refractory CE noted between and within breeds, and by extension, the potential of identifying such disease heterogeneity by DLA typing. The DLA-DQA1/DQB1 haplotype, protective against CE in our French bulldogs, has been reported as protective in various immune-mediated disorders such as Doberman hepatitis (Dyggve et al., 2011). Likewise, the DLA-DRB1006:01 risk allele for Doberman hepatitis was noted in more French bulldogs with CE compared to controls, in line with reports on genotypes associated with both risk and protection being shared across various autoimmune diseases and breeds. These findings support an immunogenetic basis to the French bulldog-CE in our analysis, calling for further DLA studies working with larger samples and different breeds towards phenotypic clarification that may aid in early diagnosis, treatment, and prophylaxis through epigenetic approaches and breeding.

摘要

犬慢性肠炎(CE)是一组病因不明的免疫遗传疾病,其特征为慢性或复发性胃肠道症状和炎症。通过治疗反应来诊断 CE 亚型是一个漫长而具有挑战性的过程,尤其是在疾病的难治性病例中。鉴于犬白细胞抗原(DLA)II 类基因型与不同品种和跨品种之间的各种免疫遗传疾病之间存在已知关联,本研究旨在通过鉴定法国斗牛犬和迷你杜宾犬(日本两种流行犬种)中与难治性 CE 相关的风险和保护基因型,来研究确定对难治性 CE 的易感性的可能性。对 29 只法国斗牛犬和 30 只迷你杜宾犬的三种 DLA II 类基因进行基于序列的基因分型,结果显示法国斗牛犬中存在一种保护性单倍型 DLA-DRB1002:01-DQA1009:01-DQB1001:01 可抵抗 CE(OR 0.09,95 % CI 0.01-0.71,p = 0.0084)。迷你杜宾犬病例与对照组之间无统计学差异。这些发现与英国对德国牧羊犬的先前研究大相径庭,这可能表明不同品种和品种之间难治性 CE 存在病因差异,并且可以通过 DLA 分型来识别这种疾病异质性。在我们的法国斗牛犬中,抵抗 CE 的 DLA-DQA1/DQB1 单倍型已在各种免疫介导的疾病中被报道为保护性的,如杜宾肝炎(Dyggve 等人,2011 年)。同样,在患有 CE 的法国斗牛犬中,DLA-DRB1006:01 风险等位基因也比对照组更为常见,这与报告的各种自身免疫性疾病和品种中同时存在风险和保护相关的基因型一致。这些发现支持我们分析中的法国斗牛犬-CE 具有免疫遗传基础,需要进一步进行 DLA 研究,使用更大的样本和不同的品种进行表型阐明,这可能有助于通过表观遗传方法和繁殖进行早期诊断、治疗和预防。

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