3型固有淋巴细胞在药物性肝损伤及自身免疫性肝炎患者中的表达具有潜在鉴别价值

肝脏 ›› 2020, Vol. 25 ›› Issue (8): 840-844.

3型固有淋巴细胞在药物性肝损伤及自身免疫性肝炎患者中的表达具有潜在鉴别价值

李青, 周天慧, 莫瑞东, 项晓刚, 赵刚德, 周惠娟, 徐玉敏, 蔡伟, 王晖, 谢青, 赖荣陶

200025 上海交通大学医学院附属瑞金医院感染科

收稿日期:2020-06-22 出版日期:2020-08-31 发布日期:2020-09-04
通讯作者: 赖荣陶,Email:lairongtao1202@163.com
基金资助:
国家“十三五”科技重大专项(2017ZX10202202-005-004,2017ZX10203201-008);国家自然科学基金资助项目(81600463;81970514);上海市临床重点专科(shslczdzk01103)。

The expression of type 3 innate lymphocytes in blood may have potential differential diagnosis value between drug-induced liver injury and autoimmune hepatitis

LI Qing, ZHOU Tian-hui, MO Rui-dong, XIANG Xiao-gang, ZHAO Gang-de, ZHOU Hui-juan, XU Yu-min, CAI Wei, WANG Hui, XIE Qing, LAI Rong-tao

Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China

Received:2020-06-22 Online:2020-08-31 Published:2020-09-04
Contact: LAI Rong-tao, Email: lairongtao1202@163.com

摘要/Abstract

摘要： 目的药物性肝损伤(DILI)发病机制目前尚不完全清楚,临床诊断多依靠RUCAM因果关系评估量表,在临床实践中常与自身免疫性肝炎(AIH)诊断混淆,因此寻找DILI早期预警信号对现阶段的DILI临床诊断具有重要意义。本研究基于我们前期的工作基础,进一步探索3型固有淋巴细胞(ILC3)在DILI中的作用。方法根据2015年中华医学会肝病学分会药物性肝病学组制定的《药物性肝损伤诊治指南》,纳入DILI患者30例,AIH患者10例,健康对照(HC)10例,分别采集外周血并统计临床人口学信息。采用Ficoll密度梯度离心法分离患者及健康人的外周血单个核细胞(PBMC),相应抗体染色后采用流式细胞计数,统计各组lin-CD127⁺NKP46⁺ILC3细胞频数,分析其与肝损伤的严重程度、急慢性病程转归的相关性以及与AIH组的表达差异。结果 (1)DILI组和AIH组的PBMC中NKp46⁺ILC3的平均细胞频数百分比分别为0.011%±0.002%和0.019%±0.004%,均显著低于HC健康组(0.041%±0.003%,P<0.001);(2)DILI组的PBMC中NKp46⁺ILC3的平均细胞频数百分比显著低于AIH组,差异有统计学意义(P<0.01);(3)DILI组NKp46⁺ILC3细胞频数百分比随病情好转逐渐升高,而AIH组NKp46⁺ILC3细胞频数百分比在治疗的相同时间段内无显著变化;(4)DILI组及AIH组中ILCs的细胞频数百分比分别为0.060%±0.006%和0.074%±0.009%,均显著低于HC健康组0.162%±0.015%(P<0.001);但DILI组和AIH组间的ILCs平均细胞频数百分比差异无统计学意义(P=0.03);(5)DILI患者NKp46⁺ILC3平均细胞频数百分比与天门冬氨酸氨基转移酶(AST)、谷氨酸氨基转移酶(ALT)、总胆红素(TBil)等肝功能水平无相关性。结论 DILI患者外周血中ILC3细胞频数明显降低,显著低于AIH组和健康对照组,其细胞频数与病程相关,但与转氨酶、总胆红素等指标无关。外周血ILC3频数改变在DILI和AIH的临床鉴别中可能具有潜在价值。

关键词: 3型固有淋巴细胞, 药物性肝损伤, 自身免疫性肝炎

Abstract: Objective The pathogenesis of drug-induced liver injury (DILI) is not yet fully understood. Clinical diagnosis relies on the scores of RUCAM scale. In particular, it is often confused with the diagnosis of autoimmune hepatitis (AIH) in clinical practice. Therefore, the search for early warning signs of DILI is of great significance for clinical diagnosis of DILI. Based on our previous work, this study further explored the expression of ILC3 cells in drug-induced liver injury. Methods 30 patients with DILI, 10 patients with AIH and 10 patients with healthy control (HC) were included in the diagnosis and treatment guidelines for drug-induced liver injury in 2015. Peripheral blood was collected and clinical demographic information was described. Peripheral blood mononuclear cells (PBMC) of patients and healthy subjects were isolated by Ficoll density gradient centrifugation. After antibody staining, flow cytometry was used to count the frequency of lin-CD127⁺NKP46⁺ILC3 in each group, and analyze the correlation between DILI and AIH. Results (1) The mean cell frequency percentages of NKp46⁺ILC3 in PBMC in DILI group and AIH group were 0.011%±0.002% and 0.019%±0.004%, which were significantly lower than those in HC healthy group (0.041%±0.003%, P<0.001). (2) The mean cell frequency percentage of NKp46⁺ILC3 in PBMC of DILI group was significantly lower than that of AIH group, with statistically significant difference (P<0.01). (3) The frequency percentage of NKp46⁺ILC3 in DILI group increased gradually with the improvement of the disease, while the frequency percentage of NKp46⁺ILC3 cells in AIH group showed no significant change during the same period of treatment. (4) The frequency percentage of ILCs in DILI and AIH group was 0.060%±0.006% and 0.074±0.009, which were significantly lower than those in healthy group (0.162±0.015) (P<0.001). However, there was no significant difference of ILCs between DILI and AIH group (P=0.03). (5) The mean cell frequency percentage of NKp46⁺ILC3 in DILI patients was not correlated with the liver function level of aspartate aminotransferase (AST), glutamate aminotransferase (ALT) and total bilirubin (TBil). Conclusion The frequency of ILC3 cells in the peripheral blood of DILI patients was significantly decreased, which was significantly lower than that of AIH group and healthy control group. The cell frequency was related to the progression of disease, but was irrelevant to transaminase, total bilirubin and other biochemical markers.

Key words: Type 3 innate lymphocytes, Drug-induced liver injury, Autoimmune hepatitis

李青, 周天慧, 莫瑞东, 项晓刚, 赵刚德, 周惠娟, 徐玉敏, 蔡伟, 王晖, 谢青, 赖荣陶. 3型固有淋巴细胞在药物性肝损伤及自身免疫性肝炎患者中的表达具有潜在鉴别价值[J]. 肝脏, 2020, 25(8): 840-844.

LI Qing, ZHOU Tian-hui, MO Rui-dong, XIANG Xiao-gang, ZHAO Gang-de, ZHOU Hui-juan, XU Yu-min, CAI Wei, WANG Hui, XIE Qing, LAI Rong-tao. The expression of type 3 innate lymphocytes in blood may have potential differential diagnosis value between drug-induced liver injury and autoimmune hepatitis[J]. Chinese Hepatolgy, 2020, 25(8): 840-844.

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