含何首乌制剂致药物性肝损伤患者TCR免疫组库特征研究

TCR immune repertoire characteristics of patients with drug-induced liver injury due to Polygonum multiflorum preparations

探索含何首乌制剂致药物性肝损伤患者的免疫状态,分析其免疫特征。研究采用病例对照设计,通过重点专科监测收集含何首乌制剂致药物性肝损伤的病例,控制含何首乌制剂品种、性别、年龄、基础疾病和合并用药5个匹配因素,按照1∶1从前瞻性医院集中监测患者中匹配使用含何首乌制剂但未发生肝损伤的病例,记录2组患者的人口学信息、疾病信息、用药信息及实验室检查信息,并采集静脉血,应用高通量测序技术检测基因序列并分析2组患者T细胞受体(TCR)免疫组库特征。研究共纳入46对患者,结果显示含何首乌制剂致药物性肝损伤患者与未发生肝损伤患者TCR免疫组库在CDR3数量及克隆种类、CDR3区氨基酸序列长度、V基因与J基因丰度、V-J基因交联,以及免疫组库的多样性上均存在显著性差异,研究发现了含何首乌制剂致药物性肝损伤患者的免疫组库多样性特征及高频率V-J交联特征,为筛选用药人群以降低含何首乌制剂致肝损伤的发生提供了参考。

To explore the immune status of patients with drug-induced liver injury caused by Polygonum multiflorum preparations,and analyze their immune characteristics.Case-control design was used to collect the cases of drug-induced liver injury caused by P.multiflorum preparations through key specialized surveillance.Five matching factors,namely type of P.multiflorum preparations,gender,age,basic diseases and concomitant medication were controlled.According to the ratio of 1∶1,cases of patients who took P.multiflorum preparations but with no liver injury were monitored at prospective hospitals.The demographic information,disease information,medication information and laboratory examination information of the two groups were recorded,and venous blood was collected.The gene sequence was detected by high-throughput sequencing technology,and the characteristics of TCR immune repertoire of the two groups were analyzed.A total of 46 pairs of patients were enrolled in the study.The results showed significant differences in the number of CDR3 and clone species,the length of amino acid sequence in CDR3 region,the abundance of V gene and J gene,the cross-linking of V-J gene and the diversity of immune repertoire between patients with drug-induced liver injury and patients without liver injury.The immunohistochemical diversity and high-frequency V-J cross-linking characteristics of patients with liver injury caused by P.multiflorum preparations were found,which provided a reference for screening out drug users to reduce the occurrence of liver injury caused by P.multiflorum preparations.