Structure biology for the causative genes of atopy and order-made therapy in the environment.

环境中特应性致病基因和定制治疗的结构生物学。

• 批准号: 13470163
• 负责人: KONDO Naomi
• 金额: $ 9.22万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470163/
• 关键词: atopy; Interferon-γ; IL-12 receptor; IgE; causative genes; IL-18 receptor; インターフェロン-γ

The causative genes of allergy have been newly found and the causative molecules (protein) have been structurally analyzed.Moreover, order-made therapy have been developed.(1)IgE production suppression systems and their defects.The mutations of IL-12 receptor β2 chain gene have been identified as one of the causative genes for allergy. Some patients with high levels of IgE production had the mutations of IL-12 receptor β2 chain gene. IL-12 was not able to inhibit IgE production of the patients' peripheral blood mononuclear cells. Therefore, it was indicated that these mutations induced high levels of IgE production and allergic reactions.Next, the mutations of IL-18 receptor α2 chain gene have been identified as the causative gene for allergy. Some patients with high levels of IgE production had the mutations of IL-18 receptor α2 chain gene. IL-18 was not able to inhibit IgE production of the patients' peripheral blood mononuclear cells. Therefore, it was indicated that these mutations also induced high levels of IgE production and allergic reactions.(2)Structural analysis of the causative genes.Moreover, we have published the information of structure of HAS protein by NMR.(3)Development of order-made therapy.Furthermore, we have published the genetical classification of atopy for clinical or prevention of allergy and order-made therapy have been published.

新发现了过敏的致病基因，并对致病分子（蛋白质）进行了结构分析，并开发了定制疗法。（1）IgE产生抑制系统及其缺陷。IL-12受体β2的突变IL-12 链基因已被确定为过敏的致病基因之一。一些 IgE 产生水平较高的患者的 IL-12 受体 β2 链基因发生突变，无法抑制 IgE。因此，表明这些突变诱导了高水平的IgE产生和过敏反应。接下来，IL-18受体α2链基因的突变已被确定为过敏的致病基因。部分IgE产生水平较高的患者存在IL-18受体α2链基因突变，IL-18不能抑制患者外周血单核细胞的IgE产生。还诱导高水平的IgE产生和过敏反应。(2)致病基因的结构分析。此外，我们还通过NMR公开了HAS蛋白的结构信息。(3)定制治疗的开发。此外，我们还发表了HAS蛋白结构信息。发表了用于临床或预防过敏的特应性遗传分类以及定制治疗。

项目成果

Kato, Z., Kondo, N.et al.: "The structure and binding mode of interleukin-18"Nature Struct Biol.. 10. 966-971 (2003)

Kato, Z., Kondo, N.等人：“白介素-18的结构和结合模式”Nature Struct Biol.. 10. 966-971 (2003)

Kondo, N.et al.: "RNA editing of interleukin-12 receptor β2, 2451 C-to-U (Ala 604 Val) conversion, associated with atopy."Clin Exp Allergy. (in press).

Kondo, N. 等人：“白介素 12 受体 β2 的 RNA 编辑，2451 C-to-U (Ala 604 Val) 转换，与特应性相关。”Clin Exp Allergy（出版中）。

Kondo, N., Matsui, E., et al.: "Review : Atopy and mutations of Il-12receptor β2chain gene"Clin Exp Allergy. 31. 1189-1193 (2001)

Kondo, N., Matsui, E., et al.：“综述：Il-12 受体 β2 链基因的特应性和突变”Clin Exp Allergy。 31. 1189-1193 (2001)

Terada, T., Kondo, N.et al.: "Analysis of Ig subclass deficiency : First reported case of IgG2,IgG4,and IgA deficiency caused by deletion of Cα1,ψCγ,Cγ2,Cγ4,and C ε in a Mongoloid patient"J Allergy Clin Immunol. 108. 602-606 (2001)

Terada, T., Kondo, N.等人：“Ig 亚类缺陷分析：首例报道蒙古人种患者中因 Cα1、ψCγ、Cγ2、Cγ4 和 C ε 缺失导致 IgG2、IgG4 和 IgA 缺陷的病例“J 过敏临床免疫学杂志。108. 602-606 (2001)

Suzuki, K., Kondo, N.et al.: "The correlation between ovomucoid-derived peptides, human leucocyte antigen class II molecules and T cell receptor-complementarity determining region 3 compositions in patients with egg-white allergy"Clin Exp Allergy. 32. 122

Suzuki, K.、Kondo, N.等人：“蛋清过敏患者中卵类粘蛋白衍生肽、人类白细胞抗原 II 类分子和 T 细胞受体互补决定区 3 成分之间的相关性”Clin Exp Allergy。