Vychodilova Leona, Matiasovic Jan, Bobrova Olga, Futas Jan, Klumplerova Marie, Stejskalova Karla, Cvanova Michaela, Janova Eva, Osickova Jarmila, Vyskocil Mirko, Sedlinska Marketa, Dusek Ladislav, Marti Eliane, Horin Petr
Institute of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Palackého 1/3, Brno, Czech Republic.
Vet Immunol Immunopathol. 2013 Apr 15;152(3-4):260-8. doi: 10.1016/j.vetimm.2012.12.013. Epub 2013 Jan 3.
Equine insect bite hypersensitivity (IBH) is a seasonal IgE-mediated dermatosis caused by bites of insects of the genus Culicoides. A familial predisposition for the disease has been shown but, except for the MHC, the genes involved have not been identified so far. An immunogenomic analysis of IBH was performed in a model population of Old Kladruby horses, all living in the same environment. Clinical signs of IBH were used as phenotypic manifestation of IBH. Furthermore, total serum IgE levels were determined in the sera of these horses and used as an independent phenotypic marker for the immunogenetic analysis. Single nucleotide polymorphisms (SNPs) in candidate immunity-related genes were used for association analyses. Genotypes composed of two to five genes encoding interferon gamma -IFNG, transforming growth factor beta 1 -TGFB1, Janus kinase 2 -JAK2, thymic stromal lymphopoietin -TSLP, and involucrin -IVL were associated with IBH, indicating a role of the genes in the pathogenesis of IBH. These findings were supported by analysis of gene expression in skin biopsies of 15 affected and 15 unaffected horses. Two markers associated with IBH, IFNG and TGFB1, showed differences in mRNA expression in skin biopsies from IBH-affected and non-affected horses (p<0.05). Expression of the gene coding for the CD14 receptor molecule -CD14 was different in skin biopsies at p<0.06. When total IgE levels were treated as binary traits, genotypes of IGHE, ELA-DRA, and IL10/b were associated with this trait. When treated as a continuous trait, total IgE levels were associated with genes IGHE, FCER1A, IL4, IL4R, IL10, IL1RA, and JAK2. This first report on non-MHC genes associated with IBH in horses is thus supported by differences in expression of genes known to play a role in allergy and immunity.
马昆虫叮咬超敏反应（IBH）是一种由库蠓属昆虫叮咬引起的季节性IgE介导的皮肤病。该病已显示出家族易感性，但除了主要组织相容性复合体（MHC）外，迄今为止尚未确定相关基因。在所有生活在相同环境中的老克拉德鲁比马模型群体中进行了IBH的免疫基因组分析。将IBH的临床症状用作IBH的表型表现。此外，测定了这些马血清中的总血清IgE水平，并将其用作免疫遗传学分析的独立表型标记。候选免疫相关基因中的单核苷酸多态性（SNP）用于关联分析。由编码干扰素γ -IFNG、转化生长因子β1 -TGFB1、Janus激酶2 -JAK2、胸腺基质淋巴细胞生成素 -TSLP和内披蛋白 -IVL的两到五个基因组成的基因型与IBH相关，表明这些基因在IBH发病机制中起作用。对15匹患病马和15匹未患病马的皮肤活检组织进行基因表达分析，支持了这些发现。与IBH相关的两个标记物IFNG和TGFB1在受IBH影响和未受影响马的皮肤活检组织中的mRNA表达存在差异（p<0.05）。编码CD14受体分子 -CD14的基因在皮肤活检组织中的表达差异为p<0.06。当将总IgE水平视为二元性状时，IGHE、ELA-DRA和IL10/b的基因型与该性状相关。当视为连续性状时，总IgE水平与基因IGHE、FCER1A、IL4、IL4R、IL10、IL1RA和JAK2相关。因此，关于马中与IBH相关的非MHC基因的这一首次报告得到了已知在过敏和免疫中起作用的基因表达差异的支持。
