原发性胆汁性胆管炎患者外周血Treg/Th17细胞相关细胞因子水平变化*

doi:10.3969/j.issn.1672-5069.2022.05.017

摘要/Abstract

摘要： 目的探讨外周血调节性T淋巴细胞(Treg)/辅助性T淋巴细胞17(Th17)相关细胞因子评估原发性胆汁性胆管炎(PBC)显著性肝纤维化的价值。方法 2019年1月～2021年12月我院收治的PBC患者59例和同期健康体检者59例,PBC患者均接受肝穿刺活检,使用流式细胞仪检测外周血Treg/Th17细胞百分比,采用ELISA法检测血清白细胞介素(IL)-10、IL-6和IL-17水平,应用SPSS 20.0软件绘制受试者工作特征曲线(ROC),以曲线下面积(AUC)评估各指标诊断PBC患者显著性肝纤维化的效能。结果 PBC患者外周血Treg细胞比率、Th17细胞比率和Th17/Treg细胞比值分别为(3.1±0.5)%、(5.9±0.9)%和(1.9±0.3),均显著高于健康人【分别为(1.6±0.3)%、(2.3±0.5)%和(1.4±0.1),P＜0.05】;PBC患者血清IL-10、IL-6和IL-17水平分别为(19.5±3.4)ng/L、(10.3±2.2)ng/L和(21.2±3.1)ng/L,均显著高于健康人【分别为(13.9±2.7)ng/L、(6.4±1.5)ng/L和(5.1±0.9)ng/L,P＜0.05】;肝组织病理学检查显示,本组PBC患者存在非显著性肝纤维化20例,显著性肝纤维化组39例;显著性肝纤维化患者外周血Treg细胞比率、Th17细胞比率和Th17/Treg细胞比值均显著高于非显著性肝纤维化患者(P＜0.05);显著性肝纤维化患者血清IL-10、IL-6和IL-17水平均显著高于非显著性肝纤维化患者(P＜0.05);经ROC曲线分析结果显示,联合外周血Treg细胞比率、Th17细胞比率、Treg/Th17比值、血清IL-10、IL-6和IL-17水平等6项指标诊断PBC患者显著性肝纤维化的AUC为0.956,显著高于六项指标的单独评估(分别为0.760、0.746、0.776、0.747、0.736和0.769,P＜0.05)。结论 PBC患者外周血Treg和Th17细胞及其细胞因子水平发生了显著的变化,而这种变化高度提示肝纤维化的存在,其诊断肝纤维化的应用值得进一步研究。

关键词: 原发性胆汁性胆管炎, 肝纤维化, 调节性T淋巴细胞, 辅助性T淋巴细胞, 细胞因子, 诊断

Abstract: Objective The aim of this study was to explore the diagnostic efficacy of peripheral blood regulatory T cells (Treg)/helper T cells 17 (Th17) and theirrelated cytokines in predicting significant liver fibrosis in patients with primary biliary cholangitis (PBC). Methods 59 patients with PBC and 59 healthy persons were encountered in our hospital between January 2019 and December 2021. All PBC patients underwent routine liver biopsy. The percentages of peripheral blood Treg/Th17 cells were detected by flow cytometry. Serum IL-10, IL-6 and IL-17 levels were detected by ELISA. The receiver operating characteristic (ROC) curves were drawn by SPSS 20.0 software, and the diagnostic performance of peripheral blood Treg/Th17 cell’s parameters in predicting significant liver fibrosis was evaluated by area under the curve (AUC). Results The percentages of peripheral blood Treg and Th17 cells, and Th17/Treg cell ratio in patients with PBC were(3.1±0.5)%, (5.9±0.9)% and (1.9±0.3), all significantly higher than [(1.6±0.3)%, (2.3±0.5)% and (1.4±0.1), respectively, P＜0.05] in healthy persons; serum IL-10, IL-6 and IL-17 levels in patients with PBC were (19.5±3.4)ng/L, (10.3±2.2)ng/L and (21.2±3.1)ng/L, all significantly higher than [(13.9±2.7)ng/L, (6.4±1.5)ng/L and (5.1±0.9)ng/L, respectively, P＜0.05] in healthy persons; the liver histopathological examination showed non-significant liver fibrosis in 20 cases, and significant liver fibrosis in 39 cases in our series; the percentages of cells and their related serum cytokine levels in patients with significant liver fibrosis were much higher than in those with non-significant liver fibrosis(P＜0.05); the ROC analysis demonstrated that the AUC was 0.956 when all the six parameter combination in predicting significant liver fibrosis in patients with PBC, much higher than 0.760, 0.746, 0.776, 0.747, 0.736 and 0.769 (P＜0.05) by any one of them. Conclusion The percentages of peripheral blood Treg and Th17 cells, and their related serum cytokine levels increase in patients with PBC, which might be related to liver fibrosis, and needs further investigation.

Key words: Primary biliary cholangitis, Liver fibrosis, Regulatory T cell, Helper T cell, Cytokines, Diagnosis

骆苏彦, 李婷婷, 王亚奇, 齐林. 原发性胆汁性胆管炎患者外周血Treg/Th17细胞相关细胞因子水平变化^*[J]. 实用肝脏病杂志, 2022, 25(5): 673-676.

Luo Suyan, Li Tingting, Wang Yaqi,et al.. Diagnostic performance of peripheral blood Treg/Th17 cells and their related cytokines in predicting significant liver fibrosis in patients with primary biliary cholangitis[J]. Journal of Practical Hepatology, 2022, 25(5): 673-676.

参考文献

[1]Lee BT, Wang Y, Yang A, et al. IgG:IgMratios of liver plasma cells reveal similar phenotypes of primary biliary cholangitis with and without features of autoimmune hepatitis. Clin Gastroenterol Hepatol, 2021, 19(2):397-399.
[2]Leung KK, Deeb M, Hirschfield GM.Pathophysiology and management of primary biliary cholangitis. Aliment Pharmacol Ther, 2020, 52(7):1150-1164.
[3]Hayashi M, AbeK, Fujita M, et al. Serum Gas6 and Axl as non-invasive biomarkers of advanced histological stage in primary biliary cholangitis. Hepatol Res, 2020, 50(12):1337-1346.
[4]Zhou Y, Yang X, Zhang H, et al. The roles of T helper type 17/regulatory T cells in acute rejection after liver transplantation in rats. Transplantation, 2015, 99(6):1126-31.
[5]Seitz T, Hellerbrand C. Role of fibroblast growth factor signalling in hepatic fibrosis. Liver Int, 2021, 41(6):1201-1215.
[6]Koda Y, Teratani T, Chu PS, et al. CD8⁺ tissue-resident memory T cells promote liver fibrosis resolution by inducing apoptosis of hepatic stellate cells. Nat Commun, 2021, 12(1):4474.
[7]中华医学会肝病学分会, 中华医学会消化病学分会, 中华医学会感染病学分会. 原发性胆汁性肝硬化(又名原发性胆汁性胆管炎)诊断和治疗共识(2015年). 中华肝脏病杂志, 2016, 24(1):5-13.
[8]Vlachogiannakos J, Binas J, Siakavellas S, et al. Platelet activation and hypercoagulability in patients with early primary biliary cholangitis compared with healthy controls. Ann Gastroenterol, 2021, 34(2):229-234.
[9]吴冬秋, 崔丽华, 熊峰, 等. 血清IL-34联合超声弹性成像诊断慢性乙型肝炎患者肝纤维化的效能分析. 实用肝脏病杂志, 2021, 24(1):23-26.
[10] John BV, Aitcheson G, Schwartz KB, et al. Male sexis associated with higher rates of liver-related mortality in primary biliary cholangitis and cirrhosis. Hepatology, 2021, 74(2):879-891.
[11] Galoosian A, Hanlon C, Zhang J, et al. Clinical updates in primary biliary cholangitis: Trends, epidemiology, diagnostics, and new therapeutic approaches. J Clin Transl Hepatol, 2020, 8(1):49-60.
[12] 黄平, 曾霞, 张亚萍, 等. 肝静脉波形分型联合肝脏超声半定量评分对慢性乙型肝炎患者肝纤维化程度评估价值研究. 实用肝脏病杂志, 2022, 25(2):187-190.
[13] Kawakami R, Kitagawa Y, Chen KY, et al. Distinct Foxp3 enhancer elements coordinate development, maintenance, and function of regulatory T cells. Immunity, 2021, 54(5):947-961
[14] Langhans B, Nischalke HD, Krämer B, et al. Role of regulatory T cells and checkpoint inhibition in hepatocellular carcinoma. Cancer Immunol Immunother, 2019, 68(12):2055-2066.
[15] He B, Wu L, Xie W, et al. The imbalance of Th17/Treg cells is involved in the progression of nonalcoholic fatty liver disease in mice. BMC Immunol, 2017, 18(1):33.
[16] Zhao S, Xu W, Xie YX, et al. CXCR5⁺ CD4⁺T cell subsets and their relationship to immune dysfunction in chronic hepatitis B-associated liver cirrhosis. J Gastroenterol Hepatol, 2020, 35(4):689-695.
[17] Crunkhorn S. Targeting TGFβ signalling in T helper cells. Nat Rev Drug Discov, 2020, 19(12):838.
[18] Basho K, Zoldan K, Schultheiss M, et al. IL-2 contributes to cirrhosis-associated immune dysfunction by impairing follicular T helper cells in advanced cirrhosis. J Hepatol, 2021, 74(3):649-660.
[19] Li X, Su Y, Hua X, et al. Levels of hepatic Th17 cells and regulatory T cells upregulated by hepatic stellate cells in advanced HBV-related liver fibrosis. J Transl Med, 2017, 15(1):75.
[20] 张辉, 张赓. 外周血中Th17/Treg与慢性乙型肝炎患者乙肝病毒DNA载量的相关性. 广东医学, 2019, 40(16):2345-2349.

原发性胆汁性胆管炎患者外周血Treg/Th17细胞相关细胞因子水平变化^*

Diagnostic performance of peripheral blood Treg/Th17 cells and their related cytokines in predicting significant liver fibrosis in patients with primary biliary cholangitis

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