免疫组库及高通量分析技术在原发性胆汁性胆管炎中的研究进展

摘要

原发性胆汁性胆管炎(PBC)是一种器官特异性自身免疫性肝脏疾病,发病机制尚不明确.T淋巴细胞受体(TCR)和B淋巴细胞受体(BCR)互补决定区3氨基酸组成和排列顺序呈现高度多样性,构成容量巨大的抗原识别受体库,即免疫组库.采用第二代测序技术结合多重PCR或扩增子救援多重PCR技术研究PBC患者免疫组库特征是近年的研究热点,目前发现PBC存在特异性CD4+T淋巴细胞大量克隆扩增,B淋巴细胞克隆多样性、体细胞高频突变及类别转换现象明显减少,熊去氧胆酸治疗后克隆多样性增加.上述发现有待通过大范围体内和体外试验及不同的免疫组库研究策略进行验证.%Primary biliary cholangitis (PBC) is an autoimmune liver disease with unclear pathogenesis.The amino acid composition and sequence in the complementarity-determining region 3 of T cell receptor (TCR) and B cell receptor (BCR) are highly diverse, which forms a large antigen recognition receptor repertoire, i.e., immune repertoire.In recent years, second-generation sequencing techniques combined with multiplex PCR or amplicon rescue multiplex PCR have been used to study the features of immune repertoire in PBC patients, and it has been found that PBC patients have clonal expansion of specific CD4+ T lymphocytes, clonal diversity of B lymphocytes, somatic hypermutation, and reduction in class switch, as well as increase in clonal diversity after treatment with ursodeoxycholic acid.These findings need to be confirmed by large-scale in vivo and in vitro studies and different immune repertoire research strategies.