Development of Novel Therapies for Canine A topic Dermatitis

犬A主题皮炎新疗法的开发

• 批准号: 10556070
• 负责人: TSUJIMOTO Hajime
• 金额: $ 7.87万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10556070/
• 关键词: Dog; Atopic dermatitis; House dust mite; Japanese cedar pollen; IgE; T-cell epitope; DNA vaccine; 皮内反応; 血清中抗原特異的IgE検査; 主要抗原; リンパ球細胞株

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.

为开发犬特应性皮炎的新疗法，开展了一系列基础和应用研究。皮内皮肤试验（IDST）和血清过敏原特异性IgE试验结果表明，房尘螨和杉木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。半数犬特应性皮炎室内尘螨的主要过敏原为Der f1、Der p1、Der f2和Der p2。在杉木花粉致敏病例中，Cry j1是多数病例的主要过敏原，Cry j2也是三分之一病例的主要过敏原。过敏原特异性t淋巴细胞发育试验表明外周血t淋巴细胞对过敏原有反应，经IDST和过敏原特异性IgE试验证实。此外，利用合成的Cry j1和Der f2肽进行t淋巴细胞胚发生试验，发现了t细胞识别这些主要过敏原的几个表位。在这些基础研究的基础上，我们进行了以插入Cry j1基因的质粒载体制备Cry j1 DNA疫苗的有效性研究。Cry j1 DNA疫苗对狗没有任何副作用。注射Cry j1 DNA疫苗可显著抑制对杉木花粉敏感的犬的特应性皮炎症状，即使在其授粉季节也是如此。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。

项目成果

Masuda,K. et al.: "IgE sensitivity and cross-reactivity to crude and purified mite allergens (Der f1, Der f2, Der p1, Der p2) in atopic dogs sensitive to Dermatophagoides mite allergens."Vet.Immunol.Immunopathol.. 72. 303-313 (1999)

增田，K.

Masuda,K. et al.: "IgE-reactivity to major Japanese cedar (Cryptomeria japonica) pollen allergens (Cry j1 and Cry j2) by ELISA in dogs with atopic dermatitis."Vet.Immunol.Immunopathol.. (印刷中). (2000)

Masuda, K. 等人：“通过 ELISA 检测患有特应性皮炎的狗对主要日本雪松 (Cryptomeria japonica) 花粉过敏原（Cry j1 和 Cry j2）的 IgE 反应性。”Vet.Immunol.Immunopathol..（出版中）。 (2000)

Sakaguchi, M.et al.: "Sensitization of grass, ragweed, mugwort pollen allergens in Japanese monkey (Macaca fuscata) : Preliminary report."Clin.Exp.Allergy. 29. 1692-1695 (1999)

Sakaguchi, M.et al.：“日本猴（Macaca fuscata）对草、豚草、艾蒿花粉过敏原的敏感性：初步报告。”Clin.Exp.Allergy。

Sakaguchi, M.et al.: "The incidence of Japanese cedar pollinosis and sensitization to the pollen allergens among Japanese monkeys in a troop."Immunology. 97. 348-351 (1999)

Sakaguchi, M.et al.：“日本雪松花粉病的发生率和日本猴子对花粉过敏原的敏感性。”免疫学。

Masuda,K.et al.: "IgE-reactivity to major Japanese cedar (Cryptomeria japonica) pollen allergens (Cry j1 and Cry j2) by ELISA in dogs with atopic dermatitis"Vet.Immunol.Immunopathol.. (印刷中). (2000)

Masuda, K. 等人：“通过 ELISA 检测患有特应性皮炎的狗对主要日本柳杉 (Cryptomeria japonica) 花粉过敏原（Cry j1 和 Cry j2）的 IgE 反应性”Vet.Immunol.Immunopathol..（出版中）。 ）