The mechanism of hepatocyte injury in chronic hepatitis B

慢性乙型肝炎肝细胞损伤机制

• 批准号: 07670622
• 负责人: KATO Tatsuko
• 金额: $ 0.32万
• 依托单位: Tokyo Women's Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670622/
• 关键词: chronic hepatitis B; pre-S2-type; CTL; Pre-S2タイプ; HBV

To elucidate the precise mechanisms of the generation of chronic hepatitis B,we first examined the uncleotide sequences of HBV and found that the pre-S2 region of hepatitis B virus (HBV) was classified into three types according to their nucleotide sequences. Subsequently, we examined the pre-S2 type in 45HBV-infected chronic hepatitis B patients together with HLA class I phenotype and disease activity. The HLA-A24 antigen was found in 27 of 32 type I pre-S2 HBV-infected patients with active hepatitis, whereas of 6 patients with inactive disease, none had HLA-A24. Serial studies in 13 patients with HLA-A24 showed that with remission of hepatitis, clearance of type I pre-S2 HBV was seen in all patients. Furthermore, we were successful to establish the CTL clones that recognize the molecular complex composed by HLA-A24 and the pre-S2 peptide. These results suggest that HLA-A24 expression in the setting of type I pre-S2 HBV infection may play a role in the pathogenesis of chronic hepatitis B.

为了阐明慢性B肝炎发生的确切机制，我们首先对乙型肝炎病毒（HBV）核苷酸序列进行了分析，发现HBV前S2区根据核苷酸序列可分为三种类型。随后，我们检测了45例HBV感染的慢性B型肝炎患者的前S2型，同时检测了HLA I类表型和疾病活动性。在32例活动性肝炎患者中，27例发现HLA-A24抗原，而在6例非活动性肝炎患者中，无HLA-A24抗原。在13例HLA-A24患者中进行的系列研究表明，随着肝炎的缓解，在所有患者中均观察到I型pre-S2 HBV的清除。此外，我们成功地建立了识别HLA-A24和pre-S2肽组成的分子复合物的CTL克隆。这些结果表明，HLA-A24在I型前S2 HBV感染的背景下的表达可能在慢性B型肝炎的发病机制中发挥作用。