Nakamura Minoru, Takii Yasushi, Ito Masahiro, Komori Atsumasa, Yokoyama Terufumi, Shimizu-Yoshida Yuki, Koyabu Makiko, Matsuyama Mutsumi, Mori Tsuyoshi, Kamihira Takashi, Daikoku Manabu, Migita Kiyoshi, Yatsuhashi Hiroshi, Nozaki Naohito, Shimoda Shinji, Ishibashi Hiromi
Clinical Research Center, National Hospital Organization, Nagasaki Medical Center, Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Kubara 2-1001-1, Omura, Nagasaki 856-8562, Japan.
J Autoimmun. 2006 Mar;26(2):138-45. doi: 10.1016/j.jaut.2005.10.007. Epub 2005 Dec 6.
The sustained antibody response to nuclear envelope gp210 antigen indicates a group of primary biliary cirrhosis (PBC) patients at high risk for the progression to end-stage hepatic failure. To address this issue, we immunohistochemically studied the expression of gp210 antigen in needle liver biopsy specimens from PBC patients using a monoclonal antibody specific for gp210 antigen. The specimens from autoimmune hepatitis (AIH), chronic viral hepatitis B (CHB) and C (CHC) patients served as disease controls. The expression of gp210 antigen was apparently increased on the nuclear envelope of biliary epithelial cells (BECs) of small bile ducts in almost all specimens from PBC. In contrast, the expression of gp210 antigen was negative in BECs of small bile ducts in normal liver, while relatively weak anti-gp210 immunostaining was observed in AIH, CHC and CHB. In addition, the degree of gp210 expression in BECs of small bile ducts was positively correlated to that of portal inflammation, interface hepatitis and lobular inflammation in PBC. These results indicate that the increased expression of gp210 in small bile ducts, which is probably associated with damage to BECs by inflammation, is possibly involved in autoimmune response to gp210 leading to the progression to end-stage hepatic failure in PBC.
对核膜糖蛋白210抗原的持续抗体反应表明，一组原发性胆汁性肝硬化（PBC）患者进展至终末期肝衰竭的风险很高。为了解决这个问题，我们使用针对糖蛋白210抗原的单克隆抗体，对PBC患者肝穿刺活检标本中糖蛋白210抗原的表达进行了免疫组织化学研究。来自自身免疫性肝炎（AIH）、慢性乙型肝炎（CHB）和丙型肝炎（CHC）患者的标本作为疾病对照。在几乎所有PBC患者的标本中，小胆管的胆小管上皮细胞（BECs）核膜上糖蛋白210抗原的表达明显增加。相比之下，正常肝脏中小胆管的BECs中糖蛋白210抗原的表达为阴性，而在AIH、CHC和CHB中观察到相对较弱的抗糖蛋白210免疫染色。此外，PBC中小胆管BECs中糖蛋白210的表达程度与门脉炎症、界面性肝炎和小叶炎症的程度呈正相关。这些结果表明，小胆管中糖蛋白210表达的增加可能与炎症对BECs的损伤有关，可能参与了对糖蛋白210的自身免疫反应，导致PBC进展至终末期肝衰竭。
