不同肝组织炎症分级和纤维化分期的自身免疫性肝炎患者外周血单个核细胞TLR2和CTLA-4水平变化研究*

doi:10.3969/j.issn.1672-5069.2023.05.014

摘要/Abstract

摘要： 目的调查不同肝组织炎症分级和纤维化分期的自身免疫性肝炎(AIH)患者外周血单个核细胞(PBMCs)Toll样受体2(TLR2)和细胞毒性T淋巴细胞相关抗原4(CTLA-4)水平变化。方法 2018年6月～2022年6月我院诊治的47例AIH患者和同期50例健康人,所有AIH患者接受肝活检。抽取外周血,分离PBMCs,采用PCR法检测PBMCs TLR2和CTLA-4 mRNA水平,使用流式细胞仪检测TLR2和CTLA-4阳性的PBMCs百分比。结果 AIH患者PBMCs TLR2 mRNA水平和细胞表面TLR2阳性的PBMCs百分比分别为(1.7±0.4)和(34.2±7.9)%,均显著高于健康人【分别为(0.9±0.2)和(21.4±3.5)%,P<0.05】,而PBMCs CTLA-4 mRNA水平和细胞表面CTLA-4阳性的PBMCs百分比分别为(0.5±0.2)和(2.3±0.8)%,均显著低于健康人【分别为(1.1±0.2)和(13.7±3.9)%,P<0.05】;21例肝组织G3/G4级患者TLR2 mRNA水平和细胞表面TLR2阳性的PBMCs百分比分别为(1.9±0.3)和(37.2±5.7)%,均显著高于26例G1/G2级患者【分别为(1.5±0.3)和(30.5±6.2)%,P<0.05】,而PBMCs CTLA-4 mRNA水平和细胞表面CTLA-4阳性的PBMCs百分比分别为(0.3±0.1)和(1.9±0.6)%,均显著低于G1/G2级患者【分别为(0.7±0.2)和(2.6±0.8)%,P<0.05】;17例肝组织F3/F4期患者TLR2 mRNA水平和细胞表面TLR2阳性的PBMCs百分比分别为(1.9±0.3)和(37.6±5.3)%,均显著高于25例F1/F2期患者【分别为(1.6±0.3)和(32.9±4.2)%,P<0.05】或5例F0期患者【分别为(1.3±0.2)和(28.7±1.9)%,P<0.05】,而PBMCs CTLA-4 mRNA水平和细胞表面CTLA-4阳性的PBMCs百分比分别为(0.3±0.1)和(1.8±0.6)%,均显著低于F1/F2期患者【分别为(0.6±0.2)和(2.3±0.7)%,P<0.05】或F0期患者【分别为(0.9±0.2)和(4.2±0.4)%,P<0.05】。结论 AIH患者PBMCs TLR2 mRNA和TLR2阳性的PBMCs百分比升高,而PBMCs CTLA-4 mRNA水平和CTLA-4阳性的PBMCs百分比降低,并与肝组织炎症活动度和纤维化程度相关,值得进一步研究。

关键词: 自身免疫性肝炎, 外周血单个核细胞, Toll样受体2, 细胞毒性T淋巴细胞相关抗原4, 病理学特征

Abstract: Objective The aim of this study was to analyze the changes of peripheral blood mononuclear cell (PBMC) Toll-like receptor 2 (TLR2) and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) in patients with autoimmune hepatitis (AIH). Methods 47 patients with AIH and 50 healthy subjects were encountered in our hospital between June 2018 and June 2022, and all patients with AIH received liver biopsies. The peripheral blood was drawn for separation of PBMCs, the TLR2 and CTLA-4 mRNA in PBMCs were detected by PCR, and the percentages of TLR2 and CTLA-4 positive PBMCs were detected by flow cytometry. Results The PBMC TLR2 mRNA level and the percentage of TLR2 positive PBMCs in patients with AIH were (1.7±0.4) and (34.2±7.9)%, both significantly higher than [(0.9±0.2) and (21.4±3.5)%, respectively, P<0.05], while the PBMCs CTLA-4 mRNA level and the percentage of CTLA-4 positive PBMCs were (0.5±0.2) and (2.3±0.8)%, both significantly lower than [(1.1±0.2) and (13.7±3.9)%, respectively, P<0.05] in healthy persons; the PBMC TLR2 mRNA level and the percentage of TLR2 positive PBMCs in 21 AIH patients with grade G3/G4 were(1.9±0.3) and (37.2±5.7)%, both much higher than [(1.5±0.3) and (30.5±6.2)%, respectively, P<0.05] in 26 AIH patients with grade G1/G2, while the PBMCs CTLA-4 mRNA level and the percentage of CTLA-4 positive PBMCs were (0.3±0.1) and (1.9±0.6)%, both much lower than [(0.7±0.2) and (2.6±0.8)%, respectively, P<0.05] in patients with G1/G2; the PBMC TLR2 mRNA level and the percentage of TLR2 positive PBMCs in 17 AIH patients with stage F3/F4 were(1.9±0.3) and (37.6±5.3)%, both much higher than [(1.6±0.3) and (32.9±4.2)%, respectively, P<0.05] in 25 patients with stage F1/F2 or [(1.3±0.2) and (28.7±1.9)%, respectively, P<0.05] in 5 patients without liver fibrosis, while the PBMCs CTLA-4 mRNA level and the percentage of CTLA-4 positive PBMCs were(0.3±0.1) and (1.8±0.6)%, both much lower than [(0.6±0.2) and (2.3±0.7)%, respectively, P<0.05] in patients with stage F1/F2 or [(0.9±0.2) and (4.2±0.4)%, respectively, P<0.05] in patients with stage F0. Conclusion The PBMC TLR2 mRNA levels and the percentage of TLR2 positive PBMCs increase, and the PBMCs CTLA-4 mRNA level and the percentage of CTLA-4 positive PBMCs decrease in patients with AIH, which might be correlated to the hepatic activity index and liver fibrosis staging, and needs further investigation.

Key words: Autoimmune hepatitis, Peripheral blood mononuclear cells, Toll-like receptor 2, Cytotoxic T lymphocyte associated antigen 4, Liver pathology

黄静, 商惠民, 王菁, 周娟. 不同肝组织炎症分级和纤维化分期的自身免疫性肝炎患者外周血单个核细胞TLR2和CTLA-4水平变化研究^*[J]. 实用肝脏病杂志, 2023, 26(5): 658-661.

Huang Jing, Shang Huimin, Wang Jing, et al. Changes of peripheral blood mononuclear cell TLR2 and CTLA-4 in patients with autoimmune hepatitis[J]. Journal of Practical Hepatology, 2023, 26(5): 658-661.

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不同肝组织炎症分级和纤维化分期的自身免疫性肝炎患者外周血单个核细胞TLR2和CTLA-4水平变化研究^*

Changes of peripheral blood mononuclear cell TLR2 and CTLA-4 in patients with autoimmune hepatitis

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