Canine immune-mediated polyarthritis (IMPA) is an idiopathic disorder encompassing both erosive and non-erosive forms of rheumatoid arthritis (RA), with a clinical picture similar to human RA. Resemblance in major histocompatibility complex (MHC)-associated risk between the two was first noted within the specific amino acid motif known as the shared epitope (SE) on human leukocyte antigen DRB1. Following further identification of amino acids conferring risk for human RA outside the SE, this study was designed to examine amino acids both within and outside the classic SE in dachshunds, a breed with reported susceptibility to IMPA in Japan. Genome-wide association studies have linked positions 11, 13 and 71 with strong risk for human RA and important roles in antigen presentation to T cells. Sequence based genotyping of 16 case and 64 control dachshunds revealed strong associations comparable to human RA between IMPA risk and valine at position 11 (Val-11), phenylalanine at 13 (Phe-13), and arginine at 71 (Arg-71) on the dog leukocyte antigen (DLA)-DRB1 molecule (OR 2.89, 95%CI 1.3–6.4, p = 0.009), while association with the classic SE was significant only regarding homozygote frequency of the QRRAA haplotype—also carrying Val 11 and Phe 13 outside the SE (p = 0.04). Moreover, limited range in possible combinations of amino acids at positions 11, 13 and 71 starting with Val-11 among all DLA-DRB1 alleles registered with the GenBank and IPD-MHC canine databases, suggested potential of further single-breed analyses in dachshunds to clarify the disorder in terms of diagnosis, treatment, and epigenetic control, while clinical and immunopathogenetic similarities between human and dachshund RA also suggested the possibility of gaining insight into RA per se through study of canine IMPA as a spontaneous model of human RA.

犬免疫介导的多发性关节炎 (IMPA) 是一种特发性疾病，包括糜烂性和非糜烂性类风湿性关节炎 (RA)，其临床表现与人类 RA 相似。两者之间主要组织相容性复合体 (MHC) 相关风险的相似性首先在人类白细胞抗原 DRB1 上称为共享表位 (SE) 的特定氨基酸基序中被发现。在进一步鉴定出 SE 以外的人类 RA 风险的氨基酸后，本研究旨在检查腊肠犬经典 SE 内部和外部的氨基酸，据报道，腊肠犬对 IMPA 易感。全基因组关联研究已将位置 11、13 和 71 与人类 RA 的高风险以及在抗原呈递至 T 细胞中的重要作用联系起来。对 16 只病例和 64 只对照腊肠犬进行的基于序列的基因分型显示，IMPA 风险与第 11 位缬氨酸 (Val-11)、第 13 位苯丙氨酸 (Phe-13) 和第 71 位精氨酸 (Arg-71) 之间存在与人类 RA 类似的强关联。狗白细胞抗原 (DLA)-DRB1 分子（OR 2.89，95%CI 1.3–6.4，p = 0.009），而与经典 SE 的相关性仅在 QRRAA 单倍型的纯合子频率方面显着（也携带 Val 11 和 Phe 13） SE 之外 (p = 0.04)。 此外，在 GenBank 和 IPD-MHC 犬数据库注册的所有 DLA-DRB1 等位基因中，从 Val-11 开始的第 11、13 和 71 位氨基酸的可能组合范围有限，这表明在腊肠犬中进行进一步单品种分析的潜力从诊断、治疗和表观遗传控制方面阐明了这种疾病，而人类和腊肠犬 RA 之间的临床和免疫病理遗传学相似性也表明，通过研究犬 IMPA 作为人类 RA 的自发模型，有可能深入了解 RA 本身。