Development of Novel Therapies for Canine A topic Dermatitis

为开发治疗犬特应性皮炎的新疗法，开展了一系列基础和应用研究。皮内试验(IDST)和血清变应原特异性IgE试验表明，屋尘螨和雪松花粉是犬特应性皮炎的常见过敏原。少数病例显示对食物、草和真菌过敏原敏感。犬特应性皮炎屋尘螨的主要变应原为Der f1、Der p1、Der f2和Der p2，半数病例为Der f1、Der p1、Der f2和Der p2。在对日本雪松花粉致敏的病例中，Cry j1是大多数病例的主要过敏原，而Cry j2也是其中三分之一的主要过敏原。过敏原特异性T淋巴细胞转化试验表明，经IDST和过敏原特异性IgE试验鉴定，外周血中存在对过敏原有反应的T淋巴细胞。此外，用Cry J1和Der f2的合成肽进行T淋巴细胞转化试验，发现了这些主要变应原的几个T细胞识别的表位。在这些基础研究的基础上，我们开展了以Cry J1基因插入载体为载体制备的Cry J1 DNA疫苗的免疫效果试验。Cry J1 DNA疫苗在狗身上没有引起任何副作用。即使在日本雪松花粉授粉的季节，注射Cry J1 DNA疫苗也能显著抑制对日本雪松花粉致敏的狗的特应性皮炎症状。目前的研究表明，主要变应原DNA疫苗是治疗犬特应性皮炎的一种新方法。

A series of basic and applied studies were carried out to develop novel therapies for canine atopic dermatitis. Intradermal skin test (IDST) and serum allergen-specific IgE test indicated that house dust mite and Japanese cedar pollen were common allergens in atopic dermatitis in dogs. A few cases were shown to be sensitized to food, grass, and fungus allergens. Major allergens of house dust mites in canine atopic dermatitis were found to be Der f1, Der p1, Der f2, and Der p2 in half of the cases. In the cases sensitized to Japanese cedar pollen, Cry jl was a major allergen in most cases and Cry j2 was also a major allergen in one third of them. A test for the allergen-specific T-lymphocyte blastogenesis indicated the presence of peripheral blood T-lymphocytes reactive to allergens which had been identified by IDST and allergen-specific IgE test. Furthermore, T-lymphocyte blastogenesis test using synthetic peptides of Cry j1 and Der f2 revealed several epitopes of these major allergens recognized by T-cells. Based on these basic researches, we carried out a trial to investigate the efficacy of Cry j1 DNA vaccine prepared from a plasmid vector with Cry j1 gene insert. The Cry j1 DNA vaccine did not induce any side effect in dogs. Injection of the Cry j1 DNA vaccine markedly suppressed the symptoms of atopic dermatitis in dogs sensitized to Japanese cedar pollen even in the season of its pollination. The present studies indicate that DNA vaccine of major allergen is a candidate of the novel therapy for canine atopic dermatitis.