Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
Genomic Information Analysis Unit, Department of Genomic Cohort Research, Faculty of Medicine, Yamagata University, Yamagata, Japan.
PLoS One. 2024 Aug 19;19(8):e0308912. doi: 10.1371/journal.pone.0308912. eCollection 2024.
Multiple factors are involved in the pathogenesis of primary biliary cholangitis (PBC), a chronic cholestatic liver disease, characterized by intrahepatic cholangiopathy. In particular, studies have suggested that environmental factors such as the presence of granulomas in the portal vein region are important for the development of PBC. This study aimed to comprehensively analyze and identify foreign-derived antigens in PBC liver tissue to confirm their involvement in PBC pathogenesis.
Portal areas and hepatocyte regions were selectively dissected from formalin-fixed paraffin-embedded PBC liver tissue samples using the microlaser method, followed by total DNA extraction. We then validated whether the bacterial strains identified through 16S rRNA metagenomic analysis were detected in PBC liver tissues.
The most frequently detected bacterial genera in the PBC liver tissue samples were Sphingomonas panacis, Providencia, and Cutibacterium. These bacterial genera were also detected in the other PBC samples. Validation for the detection of S. panacis, the most abundant genus, revealed polymerase chain reaction bands extracted from the portal areas of all samples. They were also more highly expressed than bands detected in the hepatocyte region.
S. panacis antigen was specifically detected in the portal areas of PBC liver tissues. The introduction of foreign-derived antigens into the liver as an environmental factor could be a possible mechanism for the development of PBC.
原发性胆汁性胆管炎(PBC)是一种慢性胆汁淤积性肝病,其特征为肝内胆管病。多种因素参与其发病机制,特别是研究表明门静脉区域存在肉芽肿等环境因素对于 PBC 的发生发展非常重要。本研究旨在全面分析和鉴定 PBC 肝组织中的外来抗原,以确认其在 PBC 发病机制中的作用。
使用微激光方法从福尔马林固定石蜡包埋的 PBC 肝组织样本中选择性分离门静脉区和肝细胞区,然后提取总 DNA。我们随后验证通过 16S rRNA 宏基因组分析鉴定的细菌菌株是否存在于 PBC 肝组织中。
PBC 肝组织样本中最常检测到的细菌属为 Sphingomonas panacis、Providencia 和 Cutibacterium。这些细菌属也存在于其他 PBC 样本中。对最丰富的属 Sphingomonas panacis 的检测验证显示,所有样本门静脉区提取的聚合酶链反应(PCR)带均被检测到。它们的表达水平也高于在肝细胞区检测到的带。
S. panacis 抗原特异性地在 PBC 肝组织的门静脉区被检测到。作为环境因素,外来抗原的引入可能是 PBC 发生的一种可能机制。