Studies of anti-FcepsilonRI autoantibodies in non-remitting allergic diseases.

非缓解性过敏性疾病中抗 FcepsilonRI 自身抗体的研究。

• 批准号: 09670881
• 负责人: HIDE Michihiro
• 金额: $ 1.79万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670881/
• 关键词: Allergy; The high affinity IgE receptor; Urticaria; Atopic Dermatitis; Autoantibody; Mast cell; Histamine; Transfection; 高親和性IpE受容体; 蓴麻疹; アレルギー性鼻炎

In order to analyze histamine releasing autoantibodies in diseases associated with type I allergy performed skin test by autologous sera for patients with chronic urticaria (134), allergic rhinitis (43) atopic dermatitis (70) and healthy controls (114). Fifty-six(42.4%), 0(0%), 3(4.3%) and 2(2.6%) of them showed positive reactions. Serum histamine concentrations of patients with urticaria and those atopic dermatitis were higher than those of healthy controls, but cellular histamine contents were I in patients with urticaria and higher in patients with atopic dermatitis than healthy controls. These results suggested disease specificity of the histamine releasing autoantibodies for urticana and increase of the total amount of cellular and serum histamine in patient with atopic dermatitis. We treated patient with sever chronic urticaria by double diffusion plasmapheresis with reasonable effects. Histamine release test with basophils derived from a healthy volunteer showed sera of approximately 70.4% of the patients with positive skin test by their autologous sera showed apparent histamine releasing activities with predominance of anti-FcepsilonRI type over anti-IgE type activities. In order develop a convenient method for the detection of the autoantibodies, we introduced chimeric FcepsilonRI consisting of human extracellular domain and rat trausmembrane and intracellular domains o receptor into a rat mast cell line (RBL-3D4). The cell line stably expresses the extracellular domain c human FcepsilonRI alpha-subunit and degranulated in response to either anti-FcepsilonRI monoclonal antibody or of patients with chronic urticaria. A pilot screening of the sera of urticaria suggested the cell line is : specific and easy to use than human basophils, but less sensitive. The way of application of this cel for studies of the autoantibodies and the improvement of the sensitivity is a subject for future investigations.

为了分析与 I 型过敏相关的疾病中组胺释放的自身抗体，对慢性荨麻疹 (134)、过敏性鼻炎 (43)、特应性皮炎 (70) 和健康对照 (114) 患者进行自体血清皮试。其中56例（42.4%）、0例（0%）、3例（4.3%）和2例（2.6%）呈阳性反应。荨麻疹患者和特应性皮炎患者的血清组胺浓度均高于健康对照者，但荨麻疹患者和特应性皮炎患者的细胞组胺含量均高于健康对照者。这些结果表明，荨麻疹释放组胺自身抗体的疾病特异性以及特应性皮炎患者细胞和血清组胺总量的增加。我们采用双扩散血浆置换术治疗严重慢性荨麻疹患者，效果良好。对来自健康志愿者的嗜碱性粒细胞进行的组胺释放试验显示，约70.4%的自体血清皮试呈阳性的患者的血清显示出明显的组胺释放活性，其中抗FcepsilonRI型活性优于抗IgE型活性。为了开发检测自身抗体的便捷方法，我们将由人细胞外结构域和大鼠跨膜和细胞内结构域受体组成的嵌合FcepsilonRI引入大鼠肥大细胞系（RBL-3D4）中。该细胞系稳定表达胞外结构域c人FcepsilonRI α亚基，并响应抗FcepsilonRI单克隆抗体或慢性荨麻疹患者而脱颗粒。对荨麻疹血清的初步筛选表明该细胞系：比人类嗜碱性粒细胞特异性且易于使用，但敏感性较低。该细胞用于自身抗体研究和灵敏度提高的应用方式是未来研究的课题。

项目成果

秀 道広、他: "二重膜濾過法による血漿交換を試みた難治性蕁麻疹の1例" 日本皮膚アレルギー学会雑誌. 5(1). 61 (1997)

Michihiro Hide 等人：“使用双膜过滤进行血浆置换治疗难治性荨麻疹的病例”，日本皮肤过敏学会杂志 5(1) 61 (1997)。

M.Hide, et al: "Transfection of chimeric cDNA for human-rat FcepsilonRI into RBL-2H3 cells to bind human IgE" Jpn.J.Dermatol. 109(4)(in press). (1999)

M.Hide 等人：“将人-大鼠 FcepsilonRI 的嵌合 cDNA 转染至 RBL-2H3 细胞以结合人 IgE”Jpn.J.Dermatol。

秀道広 他: "RBL-2H3細胞へのヒト・ラットキメラFcεRl分子発現によるヒトIpE刺激反応性肥満細胞株の確立" アレルギー. 48(2.3)(印刷中). (1999)

Michihiro Hide 等人：“通过在 RBL-2H3 细胞中表达人-大鼠嵌合 FcεR1 分子来建立人 IpE 刺激的肥大细胞系”48(2.3)（出版中）。

M.Hide, et al: "A case of non-remitting chronic urticaria treated with double filtration plasmapheresis" Jpn.J.Dermatoallergol.5(1). 61 (1997)

M.Hide 等人：“用双重过滤血浆去除术治疗非缓解性慢性荨麻疹的病例”Jpn.J.Dermatoallergol.5(1)。

M.Hide, et al: "Urticaria as an autoimmune disorder and new possibilities for the treatment." Allergol. 3(6). 559-564 (1997)

M.Hide 等人：“荨麻疹作为一种自身免疫性疾病以及治疗的新可能性。”