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
纯化的抗原组份具有更广泛的交叉反应性,而不是单一的纯化抗原,似乎更适合于脱敏治疗。在免疫治疗的第一步,我们使用了从整个尘螨培养物中分离出来的纯化抗原组分,它是基于强烈的皮肤反应和对抗血清的高反应性,并被证明是非常有效的治疗效果。此外,该组分没有引起副作用,诱发哮喘和过敏反应,因此被认为是一种安全高效的治疗性抗原。我们继续分析患者免疫球蛋白或抗体亚类的变化我们还分离了小分子(4K)抗原和大分子(HM)抗原(150-155K)作为其他特征抗原。LM抗原具潜在的…HM抗原组份具有较强的免疫诱导性,易被黏膜通透,与免疫治疗有效部位发生交叉反应。该抗原适合于尘螨变态反应特异性表位的结构分析和T细胞反应的诱导。另一方面,与LM抗原交叉反应的HM抗原组份具有较高的免疫原性和激活T细胞的能力,但不诱导过敏反应。抗原组份可用于免疫治疗。然而,仅用生化方法从不同批次的螨虫培养物中制备出大量组成恒定、效力稳定的治疗性抗原似乎非常困难。因此,本文提出了一种新的研究方法本研究分离了尘螨变应原的编码基因克隆,并通过交叉杂交将免疫反应阳性克隆分为9组,对其中具有较强免疫球蛋白结合活性的MAG1、MAG44和MAG3以及较弱的IgE结合活性的MAG29(HSP70)和MAG 124进行了免疫生化鉴定。较少
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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