药物性肝损伤患者外周血淋巴细胞谱和免疫检查点受体及其配体表达变化分析

Peripheral blood lymphocyte spectrum and immune checkpoint receptor and their ligand expression in patients with drug-induced liver injury

目的分析药物性肝损伤(DILI)患者外周血淋巴细胞谱和免疫检查点受体及其配体表达变化。方法2020年3月~2023年3月我院诊治的DILI患者62例、自身免疫性肝炎(AIH)患者35例和非酒精性脂肪性肝病(NAFLD)患者40例,使用流式细胞仪检测外周血淋巴细胞谱和免疫检查点受体及其配体表达。结果DILI组外周血活化Th细胞百分比为(14.2±3.8)%,显著高于AIH组【(9.7±2.3)%,P<0.05】或NAFLD组【(8.2±2.7)%,P<0.05】,DILI组和AIH组外周血活化TC细胞百分比分别为(31.3±9.2)%和(32.2±7.7)%,显著高于NAFLD组【(22.6±5.9)%,P<0.05】,Th9细胞百分比分别为(19.7±3.3)%和(19.2±2.8)%,显著低于NAFLD组【(25.3±5.4)%,P<0.05】,DILI组和NAFLD组外周血Th1细胞百分比分别为(52.6±12.3)%和(53.2±11.8),显著高于AIH组【(43.4±10.7)%,P<0.05】;DILI组外周血ICOS表达阳性Th细胞百分比为(5.2±1.5)%,显著高于AIH组【(3.9±1.1)%,P<0.05】或NAFLD组【(1.9±0.8),P<0.05】,而AIH组CTLA-4和PD-1表达阳性Th细胞百分比分别为(37.4±5.1)%和(15.7±2.3)%,显著高于DILI组【分别为(28.3±3.4)%和(12.8±1.9)%,P<0.05】或NAFLD组【分别为(18.2±3.2)%和(10.2±1.6)%,P<0.05】。结论在DILI发病的进展期间,活化的T淋巴细胞占比增加,可能参与了适应性免疫反应发病过程。了解这些现象,对阐明DILI潜在的发病机制研究可能有帮助。

Objective The aim of this study was to investigate peripheral blood lymphocyte spectrum and immune checkpoint receptors and their ligand expression in patients with drug-induced liver injury(DILI).Methods 62 patients with DILI,35 patients with autoimmune hepatitis(AIH)and 40 patients with nonalcoholic fatty liver disease(NAFLD)were recruited in our hospital between March 2020 and March 2023,and peripheral blood lymphocyte spectrum and immune checkpoints receptors and their ligand expression were detected by FCM.Results The percentage of peripheral blood activated Th cells in patients with DILI was(14.2±3.8)%,significantly higher than[(9.7±2.3)%,P<0.05]in patients with AIH or[(8.2±2.7)%,P<0.05]in patients with NAFLD,the percentage of peripheral blood activated TC cells in patients with DILI and AIH were(31.3±9.2)%and(32.2±7.7)%,significantly higher than[(22.6±5.9)%,P<0.05]in patients with NAFLD,while the percentages of Th9 cells were(19.7±3.3)%and(19.2±2.8)%,much lower than[(25.3±5.4)%,P<0.05]in patients with NAFLD,and the percentages of Th1 cells in patients with DILI and NAFLD were(52.6±12.3)%and(53.2±11.8),much higher than[(43.4±10.7)%,P<0.05]in patients with AIH;the percentage of Th cells with ICOS expression positive in patients with DILI was(5.2±1.5)%,much higher than[(3.9±1.1)%,P<0.05]in patients with AIH or[(1.9±0.8),P<0.05]in patients with NAFLD,while the percentages of Th cells with CTLA-4 and PD-1 expression positive in patients with AIH were(37.4±5.1)%and(15.7±2.3)%,much higher than[(28.3±3.4)%and(12.8±1.9)%,respectively,P<0.05]in patients with DILI or[(18.2±3.2)%and(10.2±1.6)%,respectively,P<0.05]in those with NAFLD.Conclusion During the progress of DILI,the number of peripheral blood activated T lymphocytes increases,which might participate in the pathogenesis of this entity,and needs further investigation.