Pathogenesis of summer-type hypersensitivity pneumonitis : Analysis with serotype-related polysaccharide of Trichosporon cutaneum and its nonoclonal antibodies

夏季型过敏性肺炎的发病机制：皮肤毛孢子菌血清型相关多糖及其非克隆抗体分析

• 批准号: 03670405
• 负责人: ANDO Masayuki
• 金额: $ 1.28万
• 依托单位: Kumamoto 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: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670405/
• 关键词: Summer-type hypersensitivity pneumonitis; Trichosporon cutaneum; monoclonal antibody; enzyme-linked immunosorbent assay; glucuronoxylomannan; serotype-specific polysaccharide antigen; 診断用ELISAキット; モノクロ-ナル抗体; 菌血清型関連抗原; 発症機序; 気管支肺胞洗浄液

Summer-type hypersensitivity pneumonitis (SHP) is a unique type of hypersensitivity pneumonitis and the most prevalent in Japan. Our previous study clarified that the causative agent of the disease is Trichosporon cutaneum, and that the patients with SHP have high titer of antibodies against the serotype-specific antigen of polysaccharide nature which exist in the high molecular weight fraction of the culture supernatant of the yeast. In this study, we purified the serotype-specific antigen of serotype II T.cutaneum by gel filtration and affinity chromatography using a monoclonal antibody, D-8, specific for serotype II T.cutaneum, and elucidated the structure of the antigen. The affinity-purified antigen was shown to be essentially acidic polysaccharide comprising mannose, xylose, and glucuronic acid. Chemical analysis showed that this polysaccharide antigen contains a (1-3)-linked mannan backbone attached with short chains of (1-4)-linked mannose and a small portion of (1-2) linked xylose residues by substituting the 2-or4- positions of the (1-3)-linked mannose residues of the main chain. The antigenic epitope was shown to involve the terminal glucuronic acid residues as revealed by immunodiffusion test and sandwich enzyme-linked immunosorbent assay using monoclonal antibody D-8.

夏季型超敏性肺炎（SHP）是一种独特的超敏性肺炎，在日本最为流行。我们前期的研究明确了该疾病的病原体是皮肤毛霉，并且SHP患者对多糖性质的血清型特异性抗原具有高滴度的抗体，这种抗体存在于酵母培养上清的高分子量部分中。本研究采用凝胶过滤和亲和层析的方法纯化了血清II型T.cutaneum血清型特异性抗原，并鉴定了抗原的结构。亲和纯化抗原被证明本质上是酸性多糖，包括甘露糖、木糖和葡萄糖醛酸。化学分析表明，该多糖抗原含有(1-3)-连接的甘露糖主链，通过取代(1-3)-连接的甘露糖残基的2-或4-位置，连接(1-4)-连接的甘露糖短链和一小部分（1-2）连接的木糖残基。单克隆抗体D-8的免疫扩散试验和夹心酶联免疫吸附试验表明，抗原表位涉及末端葡萄糖醛酸残基。

项目成果

MizobeT,Yamasaki H,Doi K,Ando M.and Onoue K: "Analysis of serotype-specific antibodies to Trichosporon cutaneum Types I and II in patients with summer-type hypersensitivity pneumonitis with monoclonal antibodies to serotype-related polysaccharide antigen"

MizobeT、Yamasaki H、Doi K、Ando M.和 Onoue K：“用血清型相关多糖抗原的单克隆抗体分析夏季型过敏性肺炎患者 I 型和 II 型皮肤毛孢子菌的血清型特异性抗体”

Mizobe T,Yamasaki H,Doi K,Ando M, and Onoue K.: "Analysis of serotype-specific antibodies to Trichosporon cutaneum Types I and II in patients with summer-type hypersensitivity pneumonitis with monoclonal antibodies to serotype-related polysaccharide antig

Mizobe T、Yamasaki H、Doi K、Ando M 和 Onoue K.：“用针对血清型相关多糖抗体的单克隆抗体分析夏季型过敏性肺炎患者中 I 型和 II 型皮肤毛孢子菌的血清型特异性抗体”

Ito k, Yamasaki H,Onoue K, and Ando M.: "Experimental hypersensitivity pneumonitis in mice induced by Trichosporon cutaneum : Histopathologic and immunologic features and effect of in vitro depletion of T cell subsets." Experimental Lung Disease. 19. 631-

Ito k、Yamasaki H、Onoue K 和 Ando M.：“皮肤毛孢子菌诱导的小鼠实验性过敏性肺炎：组织病理学和免疫学特征以及体外 T 细胞亚群耗竭的影响。”