IgG class antibody to hepatic endothelial cell in sera of patients with autoimmune hepatitis and its pathophysiological significance

自身免疫性肝炎患者血清中肝内皮细胞IgG类抗体及其病理生理意义

• 批准号: 03454224
• 负责人: TODA Gotaro
• 金额: $ 3.71万
• 依托单位: The Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454224/
• 关键词: Hepatic sinusoidal endothelial cell; Autoimmune hepatitis; Anti-endothelial cell antibody; Heparin; Chronic hepatitis; 内皮細胞障害; 類洞壁内皮細胞; 血管内皮細胞; スルファチド; ヘパラン硫酸; 類洞壁内皮細胞抗体

An antibody against rat hepatic sinusoidal endothelial cells (HSECs) was identified in the serum of patients with autoimmune hepatitis (AIH). HSECs were isolated from rat liver, cultured for 18 h and fixed with glutaraldehyde. After incubation of the cells with 1 : 250 dilutions of serum from patients with AIH, chronic hepatitis type B or C, or normal healthy subjects, the amount of IgG bound was evaluated with peroxdaseconjugated protein A.In 14 of 15 patients with AIH, the amount of IgG bound to the cells exceeded the mean plus 3SD of normal healthy subjects and patients with chronic hepatitis type B and C.Treatment of the sera from AIH patients with dithiothreitol and iodoacetamide did not reduce the amount of IgG bound to HSECs. Furthermore, F(ab')2, prepared by peptic digestion of IgG from AIH patients, retained the activity to bind to HSECs. These findings indicate that the antigen determinant was a heparin-like structure on the surface of HSECs. The amount of IgG bound to the cells was significantly reduced after the patients were treated with corticosteroids. Culture of HSECs in the presence of IgG from AIH patients reduced the number of cells attached to the dish, suggesting that the antibody injured the cultured HSECs. From these results, the antibody against HSECs may contribute to the pathogenesis of AIH.

在自身免疫性肝炎（AIH）患者血清中发现一种抗大鼠肝窦内皮细胞（HSEC）的抗体。从大鼠肝脏中分离HSEC，培养18 h并用戊二醛固定。将细胞与1：用过氧化物酶偶联蛋白A评价250份来自AIH、慢性B型或C型肝炎患者或正常健康受试者的血清的IgG结合量。在15名AIH患者中的14名中，与细胞结合的IgG的量超过正常健康受试者和慢性肝炎B型和C型患者的平均值加3SD。来自AIH患者的含二硫苏糖醇和碘乙酰胺的血清不减少与HSEC结合的IgG的量。此外，通过消化来自AIH患者的IgG制备的F（ab '）2保留了与HSEC结合的活性。这些结果表明，抗原决定簇是一个肝素样结构的表面HSEC。在患者用皮质类固醇治疗后，与细胞结合的IgG的量显著减少。在存在来自AIH患者的IgG的情况下培养HSEC减少了附着于培养皿的细胞的数量，这表明抗体损伤了培养的HSEC。因此，抗HSEC抗体可能参与了AIH的发病机制。

项目成果

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S.Aotsuka 等人：“自身免疫性风湿性疾病患者血清中抗 aulphatide 的抗体”Clin.exp.Immunol.87。

Kato, Hirokazu: "Injury of endothelial cell by IgG from serum of autoimmne hepatitis patients" Proceedings of the Japan society of clinical Biochemistry and Metabolism(Vol.XXVIII). 28. 72-73 (1991)

Kato, Hirokazu：“自身免疫性肝炎患者血清中的 IgG 对内皮细胞的损伤”日本临床生物化学和代谢学会会议记录（第 XXVIII 卷）。

Toda, Gotaro: "Autoimmune liver diseases" The Journal of the Japanese Society of Internal Medicine. 82. 1403-1408 (1993)

户田吾太郎：“自身免疫性肝病”日本​​内科医学会杂志。

Toda, Gotaro: "Autoimmune hepatitis" The Journal of the Japanese Society of Internal Medicine. 83. 209-215 (1994)

户田吾太郎：“自身免疫性肝炎”日本内科医学会杂志。

Toda, Gotaro: "Autoimmune hepatitis" Japanese Journal of Gastroenterology. 90. 2059-2066 (1993)

Toda, Gotaro：“自身免疫性肝炎”日本胃肠病学杂志。