Can the Occurence of Autoantibody to Protein Disulfide Isomerase be a Marker for the Development of Hepatitis?

蛋白质二硫键异构酶自身抗体的出现可以作为肝炎发展的标志吗？

• 批准号: 05807204
• 负责人: YOKOI Tsuyoshi
• 金额: $ 1.22万
• 依托单位: Hokkaido 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: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05807204/
• 关键词: Autoimmune antibodies; LEC rats; Hepatitis; Protein disulfide isomerase; Cyclosporin-A; D-Penicillamine; カルレチクリン

(1) Long Evans Cinnamon (LEC) rats, showing spontaneous hereditary hepatitis and hepatic carcinoma, were found to possess autoimmune antibodies to liver microsomal proteins, particularly to proteis with the molecular weight of 56kD and 55kD.The antibodies occurred in association with acute lethal hepatitis in the LEC rats. These two antigenic protein were revealed to be protein disulfide isomerase (PDI) and calreticulin, respectively, from NH2-terminal amino acid sequence analysis. PDI was a major autoimmune antigenic protein.(2) The occurrence of an autoantidody to PDI in rats after administration of various hepatotoxic drugs was investigated by immunoblotting and radiommunoassay. The anti-PDI autoantibody was detected with high frequency in rats pretreated pretreated with D-galactosamine, acetaminophen with diethylmaleate, and carbon tetrachloride with diethylmaleate. The antibody-positive rate was relatively low in the groups of rats given carbon tetrachloride, acetaminophen, acetam … More inophen or DL-ethionine alone. The anti-PDI antibody was not detected in rats treated with diethylmaleate alone. Although the mechanism of the production of the anti-PDI autoantibody is unclear, the occurrence of anti-PDI antibody correlated with high serum GPT activities.(3) Cyclosporin-A,an immunosuppressant, and D-penicillamine, which promotes copper excretion, were orally administered to LEC rats for 23 weeks. Mortality, blood biochemical parameters and the titer of serum anti-PDI antibody were measured. In control LEC rats, four of eight rats died bifore 20-weeks-old. Only one of seven rats in the cyclosporin-A-treated group died at the age of 20 weeks. When rats were treated with D-penicillamine, the development of clinical signs of hepatitis was inhibited, and all rats survived. Cyclosporin-A-treated rats showed increases in blood biochemical parameters similar to those in control rats. The titer of anti-PDI antibody in control rats was higher in the non-survivors than in the survivors. These findings suggest the association of the anti-PDI antibody with lethality, but not with the apparent development and progression of hepatitis as measured by blood biochemical parameters in LEC rats. Less

（1）被发现长长的埃文斯肉桂（LEC）大鼠显示出赞助的遗传性肝炎和肝炎癌，被发现具有抗肝微粒体蛋白的自身免疫性抗体，特别是对蛋白质的蛋白质，尤其是蛋白质的分子量为56KD和55KD。从NH2-末端氨基酸序列分析中，这两种抗原蛋白分别是蛋白二硫化物异构酶（PDI）和钙网蛋白。 PDI是一种主要的自身免疫性抗原蛋白。（2）通过免疫印迹和放射线仪调查了给药各种肝毒性药物后，大鼠中PDI的自身抗体发生。在用D-半乳糖胺，乙酰氨基酚和二乙基甲基甲酸酯和二乙基甲基甲碳二氯化碳预处理的大鼠中检测到抗PDI自身抗体。给定四氯化碳，对乙酰氨基酚，乙酰氨基苯甲酸盐的大鼠组的抗体阳性速率相对较低。在单独用二乙基乳酸治疗的大鼠中未检测到抗PDI抗体。尽管抗PDI自身抗体产生的机制尚不清楚，但抗PDI抗体的发生与高血清GPT活性相关。（3）环孢菌素A，一种免疫抑制剂，一种免疫抑制剂和d-苯胺，促进铜的铜量为23周。测量了死亡率，血液生化参数和血清抗PDI抗体的滴度。在对照lec大鼠中，八只大鼠中有四只大鼠死于20周大。 Cyclosporin-A治疗组中只有七只大鼠中只有一只死于20周。当用D-苯胺胺治疗大鼠时，抑制肝炎的临床体征的发展，所有大鼠都得以幸存。环孢菌素A治疗的大鼠的血液生化参数与对照大鼠相似。对照大鼠中抗PDI抗体的滴度在非活体中高于表面。这些发现表明，抗PDI抗体与致死性的关联，但没有通过LEC大鼠的血液生化参数测量的肝炎的明显发展和进展。较少的

项目成果

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