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-DRB1*002:01-DQA1*009:01-DQB1*001:01 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-DRB1*006:01 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.

犬慢性肠病 (CE) 是一组病因不明的免疫遗传性疾病，其特征是慢性或复发性胃肠道体征和炎症。通过治疗反应诊断 CE 亚型是一个漫长且具有挑战性的过程，尤其是在该疾病的难治性病例中。鉴于狗白细胞抗原 (DLA) II 类基因型与品种之间和品种之间的各种免疫遗传疾病的已知关联，本研究旨在通过鉴定法国斗牛犬和小型腊肠犬的风险和保护性基因型来检查确定难治性 CE 易感性的潜力——日本流行的两种犬种。

对 29 只法国斗牛犬和 30 只具有难治性 CE 的微型腊肠犬的三个 DLA II 类基因的基于序列的基因分型揭示了一种保护性单倍型 DLA-DRB1*002:01-DQA1*009:01-DQB1*001:01 在法国斗牛犬中对抗 CE（ OR 0.09, 95% CI 0.01-0.71, p = 0.0084)。小型腊肠犬病例和对照之间没有发现统计学差异。这些发现与之前对英国德国牧羊犬的研究大不相同，它们被视为可能表明品种之间和品种内发现的难治性 CE 的病因差异，以及通过 DLA 分型识别此类疾病异质性的潜力。

DLA-DQA1/DQB1 单倍型，在我们的法国斗牛犬中对 CE 有保护作用，据报道在各种免疫介导的疾病中具有保护作用，例如杜宾肝炎（Dyggve 等，2011）。同样，与对照组相比，在更多患有 CE 的法国斗牛犬中发现了杜宾肝炎的 DLA-DRB1*006:01 风险等位基因，这与有关各种自身免疫疾病和品种共享的风险和保护相关基因型的报告一致。

在我们的分析中，这些发现支持法国斗牛犬 CE 的免疫遗传学基础，呼吁对更大的样本和不同品种进行进一步的 DLA 研究，以阐明表型，这可能有助于通过表观遗传方法和育种进行早期诊断、治疗和预防。