IFN-α治疗后发生HBsAg转阴的慢性乙型肝炎患者外周血免疫库谱特征分析

发布时间：2018-01-20 13:30

本文关键词： 免疫库 T细胞受体慢性乙肝感染 HBsAg转阴　出处：《免疫学杂志》2017年04期 　论文类型：期刊论文

【摘要】：目的通过对慢性乙型肝炎患者经IFN-α治疗后出现HBs Ag转阴病例与未转阴病例外周血中T细胞受体β链(TCRβ,TRB)序列分析比较,探讨HBs Ag转阴病人外周血免疫库TCRβ的特征,为预测病人临床结局以及评价治疗效果提供新的指标。方法收集HBV感染病人的外周血样进行密度梯度离心获得淋巴细胞,冻存。待IFN-α治疗一段时间后,取HBs Ag转阴病例与未转阴病例相应的冻存细胞,提取RNA,逆转录为c DNA后通过多重PCR对TCRβ链的CDR3区序列进行扩增、纯化,高通量测序后将测序结果与IMGT数据库进行比对,以找到HBs Ag转阴病人外周血TRB-CDR3免疫组库的特征,分析人外周血TRB-CDR3多样性及其他免疫学特征与HBs Ag转阴之间的关系。结果 IFN-α治疗后HBs Ag转阴的患者TRB-CDR3的多样性高于未转阴患者,并表现出其特有的免疫学特征,包括高频取用的V、J家族、V-J家族配对、基因的插入、CDR3区长度分布等均与未转阴组有明显差异,而基因的缺失方面未发现差异。结论 IFN-α治疗后HBs Ag转阴的患者的免疫组库呈现明显的免疫学特征,可为临床疗效的预测提供新的切入点。
[Abstract]:Objective to analyze and compare the sequence of T cell receptor 尾 chain TCR 尾 -tbb in peripheral blood of patients with chronic hepatitis B (CHB) treated with IFN- 伪. Objective: to investigate the characteristics of TCR 尾 in peripheral blood immune library of patients with HBs Ag turning negative. Methods Peripheral blood samples from patients with HBV infection were collected to obtain lymphocytes by density gradient centrifugation. Cryopreservation. After treatment with IFN- 伪 for a period of time, RNA was extracted from frozen cells of HBs Ag negative cases and non-negative cases. The sequence of CDR3 region of TCR 尾 chain was amplified by multiplex PCR and purified by reverse transcription to c DNA. After high throughput sequencing, the sequence results were compared with IMGT database. In order to find out the characteristics of peripheral blood TRB-CDR3 immune library in patients with HBs Ag turning negative. The relationship between TRB-CDR3 diversity and other immunological characteristics of human peripheral blood and the conversion of HBs Ag to negative was analyzed. Results HBs was treated with IFN- 伪. The diversity of TRB-CDR3 in patients with negative Ag was higher than that in patients without negative. And showed its unique immunological characteristics, including the high-frequency Vapor J family V-J family pairing, gene insertion CDR3 length distribution and so on there are significant differences between the negative group and non-negative group. Conclusion the immune group library of patients with negative HBs Ag after IFN- 伪 therapy has obvious immunological characteristics, which may provide a new entry point for the prediction of clinical efficacy.
【作者单位】：第三军医大学免疫学研究所;西南医院全军传染病研究所;
【基金】：国家自然科学基金国际(地区)合作与交流项目(81220108024)
【分类号】：R512.62
【正文快照】： 乙肝(viral hepatitis B)是由乙型肝炎病毒引起的肝炎疾病,目前仍是世界性的健康难题[1-2]。核苷类似物(UA)等药物的使用大大改善了HBV的治疗现状[3],但是并不能使大多数患者完全治愈,表现在乙肝表面抗原(HBs Ag)不能转阴。而HBs Ag的水平又与肝癌的发生发展密切相关[4]。因此

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