Application of mite allergen to desensitization immunotherapy
Application of mite allergen to desensitization immunotherapy
批准号:
05650802
负责人:
ONO Kazuhisa
金额:
$1.47万
依托单位:
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
项目状态:
已结题
起止时间:
1993 至 1994
中文摘要
与单一纯化抗原相比,具有更广泛交叉反应性的纯化抗原组合似乎更适合于脱敏治疗。在免疫治疗的第一步中使用了从整个螨培养物中分离出来的纯化抗原,该抗原是基于强烈的皮肤反应和对抗血清和对螨过敏的患者血清的高反应性,并证明了高度的治疗效果。此外,该组分未引起任何副反应,未引起哮喘和过敏反应,因此该组分已被公认为安全性和有效性高的治疗性抗原。我们正在持续分析患者免疫球蛋白或抗体亚类滴度的变化,或嗜碱性粒细胞对过敏原的敏感性与免疫治疗效果的关系。我们还分离了低分子大小(LM)抗原(4k)和高分子大小(HM)抗原(150-155k)作为其他特征抗原。LM抗原具有潜在的更强的诱导特性,易于渗透到粘膜,与免疫治疗有效的部分交叉反应。该抗原将适用于螨过敏特异性表位的结构分析和T细胞能量的诱导。另一方面,与LM抗原交叉反应的HM抗原组分具有较高的免疫原性和激活T细胞的能力,但不引起过敏反应。抗原组分可用于免疫治疗。然而,仅靠生物化学方法很难从不同批次的螨培养物中制备出数量大、成分稳定、效力稳定的治疗性抗原。因此,我们分离到了编码螨变应原的cDNA克隆,并通过交叉杂交将其分为9组。其中表达产物Mag1(高激活小鼠T细胞能力)、Mag44(原肌球蛋白)、Mag3(高激活人和小鼠T细胞能力)具有较强的ige结合活性,Mag29 (hsp70)和mag124具有较弱的ige结合活性,本研究对其进行了免疫生化表征。少
英文摘要
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
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T.Aki: "Structure of IgE epltopes on a new 39kDa allergen molecule from the house dust mite,Dermatophagoides farinae" Int.Arch.Allergy Immunol.103. 357-364 (1994)
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。
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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)。
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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)。
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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
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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。”
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