Application of mite allergen to desensitization immunotherapy

螨变应原在脱敏免疫治疗中的应用

• 批准号: 05650802
• 负责人: ONO Kazuhisa
• 金额: $ 1.47万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05650802/
• 关键词: desensitization; immunotherapy; therapeutic antigen; low-molecular-size antigen; high-molecular-size antigen; recombinant allergen; T cell actiation; mite allergen; 高分子アレルゲン; 低分子アレルゲン; 結膜反応活性; エピトープ; 39kDアレルゲン; 熱ショック蛋白質; 新規ダニアレルゲン

The combination of purified antigens with broader cross-reactivity, rather than single purified antigen, seemed to be suitable for desensitization therapy.A purified antigen fraction has been used at first step of the immunotherapy, which was isolated from a whole mite culture on the basis of potent skin reaction and high reactivity to antisera and patients' sera allergic to mite, and has proved highly therapeutic effects.Moreover, the fraction has elicited no side reaction, induction of asthma and anaphylaxis reaction, so that the fraction has been recognized as a therapeutic antigen with high safety and efficiency.Continuously, we are analyzing relationship between changes in titers of patients' immunoglobulins or antibody subclasses, or in sensitivity of basophils to allergens and the efficacy of the immunotherapy.We also isolated low-molecular-size (LM) antigen (4k) and high-molecular-size (HM) antigens (150-155k) as other characteristic antigens.The LM anttigen with potentially as … More thma-inducible property which is facilely permeable to mucosa cross-reacted with the fraction effective for immunotherapy.The antigen would be fit for structual analysis of mite-allergy specific epitopes and induction of T cell anergy.On the other hand, the HM antigen fractions cross-reactive to the LM antigen possessed high immunogenicity and ability to activate T cells, but not induced anaphylaxis reaction.The antigen fractions might be used for immunotherapy.However, it seemed very difficult to prepare a large quantity of therapeutic antigen with constant composition and stable potency from different batches of mite cultures by only biochemical methods.Thus, we isolated cDNA clones encoding mite allergen and classfied the immunoreactive clones into 9 groups by cDNA cross-hybridization.Among them, expression products, Mag1 (high ability to activate mouse T cell), Mag44 (tropomyosin), and Mag3 (high ability to activate human and mouse T cell) with potent IgE-binding activity, and Mag29 (hsp70) and Mag 124 with less IgE-binding activity, were immunobiochemically characterized in this study. Less

具有广泛交叉反应性的纯化抗原的组合似乎比单一纯化抗原更适合于脱敏治疗。纯化抗原组分已被用于免疫治疗的第一步，其是基于强皮肤反应性和对抗血清和对螨过敏的患者血清的高反应性从螨全培养物中分离的，并且已被证明具有高治疗效果。此外，该级分没有引起副反应、哮喘诱导和过敏反应，因此该级分被认为是具有高安全性和有效性的治疗性抗原。我们继续分析患者免疫球蛋白或抗体亚类的滴度变化之间的关系，我们还分离了低分子量（LM）抗原（4k）和高分子量（HM）抗原，（150- 155 k）作为其它特征性抗原。 ...更多信息 结果表明，HM抗原组分与LM抗原组分具有良好的免疫原性和激活T细胞的能力，HM抗原组分与LM抗原组分具有良好的免疫原性，HM抗原组分与LM抗原组分具有良好的免疫原性和激活T细胞的能力，HM抗原组分与LM抗原组分具有良好的免疫原性，HM抗原组分与LM抗原组分具有良好的免疫原性，HM抗原组分与LM抗原组分具有良好的免疫原性和激活T细胞的能力，HM抗原组分与LM抗原组分具有良好的免疫原性，HM抗原组分与LM抗原组分具有良好的免疫原性和激活T细胞的能力，HM抗原组分与LM抗原组分具有良好的免疫原性，HM抗原组分与LM抗原组分具有良好的免疫原性和激活T细胞的能力，HM抗原组分与LM抗原组分具有良好的免疫原性和免疫原性，HM抗原组分与LM抗原组分具有良好的免疫原性和激活T细胞的能力，HM抗原组分与LM抗原组分具有良好的免疫原性和激活T细胞的能力，HM抗原组分具有良好的免疫原性和免疫原性。但不诱导过敏反应。抗原组分可用于免疫治疗。然而，从不同批次的螨培养物中制备大量组成恒定、效价稳定的治疗性抗原，方法：通过cDNA交叉杂交，将螨变应原的cDNA克隆分为9类，其中表达产物Mag 1（高活化小鼠T细胞的能力），Mag 44（原肌球蛋白）和Mag 3（高活化人和小鼠T细胞的能力），以及具有较低IgE结合活性的Mag 29（hsp 70）和Mag 124。少

项目成果

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T.Aki：“来自屋尘螨 Dermatophagoides farinae 的新 39kDa 过敏原分子上的 IgE 表位结构”Int.Arch.Allergy Immunol.103。

T.Aki: "Cloning and characterization of cDNA coding for a new allergen from the house dust mite,Dermatophagoides farinae" Int.Arch.Allergy Immunol. (印刷中). (1994)

T.Aki：“来自屋尘螨 Dermatophagoides farinae 的 cDNA 编码的克隆和表征”Int.Arch.Allergy Nutrition（正在出版）。

T.Aki: "Immunochemical characterization of recombinant and native tropomyosins as a new allergen from the house dust mite,Dermatophagoides farinae." J.Allergy Clin.Immunol.95(印刷中). (1995)

T.Aki：“来自屋尘螨 Dermatophagoides farinae 的重组和天然原肌球蛋白的免疫化学特征。J.Allergy Clin.Immunol.95（出版中）。

Tsunehiro AKI,Akihiro FUJIKAWA,Tadashi WADA,Toshihiko JYO,Seiko SHIGETA,Yoshikatu MUROOKA,Satoru OKA,Kazuhisa ONO: "Cloning and expression of cDNA coding for a new allergen from the house dust mite, Dermatophagoides farinae.Homology with human heat shock

Tsunehiro AKI、Akihiro FUJIKAWA、Tadashi WADA、Toshihiko JYO、Seiko SHIGETA、Yoshikatu MUROOKA、Satoru OKA、Kazuhisa ONO：“来自屋尘螨 Dermatophagoides farinae 的新过敏原的 cDNA 编码的克隆和表达。与人类热休克的同源性

T.Yamaguchi: "Differences in response of patients blood cells with bronchial asthma to diverse house dust mite allergens by histamine release assay." Jpn.J.Allergol.42. 1754-1763 (1993)

T.Yamaguchi：“通过组胺释放测定，观察​​支气管哮喘患者血细胞对不同屋尘螨过敏原的反应差异。”