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乙型肝炎病毒相关肝衰竭中的黏膜相关恒定T细胞

Mucosal-associated invariant T cells in hepatitis B virus-related liver failure.

作者信息

Xue Hong, Li Han, Ju Lin-Ling, Han Xu-Dong, Cheng Tiao-Chun, Luo Xi, Chen Lin, Shao Jian-Guo, She Yong-Jun, Bian Zhao-Lian

机构信息

Department of Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong 226006, Jiangsu Province, China.

Medical School of Nantong University, Nantong 226006, Jiangsu Province, China.

出版信息

World J Gastroenterol. 2020 Aug 21;26(31):4703-4717. doi: 10.3748/wjg.v26.i31.4703.

Abstract

BACKGROUND

Liver failure has high mortality and poor prognosis, and establishing new reliable markers for predicting its prognosis is necessary. Mucosal-associated invariant T (MAIT) cells are a novel population of innate-like lymphocytes involved in inflammatory liver disease, and their potential role in liver failure remains unclear.

AIM

To investigate alteration of circulating MAIT cells and assess its prognostic value in patients with hepatitis B virus (HBV)-related liver failure.

METHODS

We recruited 55 patients with HBV-related liver failure, 48 patients with chronic hepatitis B and 40 healthy controls (HCs) from Nantong Third People's Hospital Affiliated to Nantong University. Peripheral blood mononuclear cells were isolated, and the percentage and number of circulating MAIT cells were detected by flow cytometry. Plasma levels of interleukin (IL)-7, IL-12p70, IL-18 and interferon-α were measured by Luminex assay.

RESULTS

Circulating MAIT cells were significantly decreased in HBV-related liver failure patients (percentage: 2.00 ± 1.22 5.19 ± 1.27%, 0.0001; number: 5.47 ± 4.93 84.43 ± 19.59, 0.0001) compared with HCs. More importantly, there was a significant reduction of MAIT cells in patients with middle/late-stage compared with early-stage liver failure. Circulating MAIT cells partially recovered after disease improvement, both in percentage (4.01 ± 1.21 2.04 ± 0.95%, 0.0001) and in cell count (17.24 ± 8.56 7.41 ± 4.99, 0.0001). The proportion (2.29 ± 1.01 1.58 ± 1.38%, 0.05) and number (7.30 ± 5.70 2.94 ± 1.47, 0.001) of circulating MAIT cells were significantly higher in the survival group than in the dead/liver transplantation group, and the Kaplan-Meier curve showed that lower expression of circulating MAIT cells (both percentage and cell count) predicted poor overall survival ( 0.01). Also, the levels of IL-12 (20.26 ± 5.42 pg/mL 17.76 ± 2.79 pg/mL, 0.01) and IL-18 (1470.05 ± 1525.38 pg/mL 362.99 ± 109.64 pg/mL, 0.0001) were dramatically increased in HBV-related liver failure patients compared with HCs.

CONCLUSION

Circulating MAIT cells may play an important role in the process of HBV-related liver failure and can be an important prognostic marker.

摘要

背景

肝衰竭死亡率高且预后差,因此有必要建立新的可靠标志物来预测其预后。黏膜相关恒定T(MAIT)细胞是一类新型的固有样淋巴细胞,参与炎症性肝病,其在肝衰竭中的潜在作用尚不清楚。

目的

研究循环MAIT细胞的变化,并评估其在乙型肝炎病毒(HBV)相关肝衰竭患者中的预后价值。

方法

我们从南通大学附属南通第三人民医院招募了55例HBV相关肝衰竭患者、48例慢性乙型肝炎患者和40名健康对照者(HCs)。分离外周血单个核细胞,采用流式细胞术检测循环MAIT细胞的百分比和数量。采用Luminex分析法检测血浆白细胞介素(IL)-7、IL-12p70、IL-18和干扰素-α水平。

结果

与HCs相比,HBV相关肝衰竭患者的循环MAIT细胞显著减少(百分比:2.00±1.22%对5.19±1.27%,P<0.0001;数量:5.47±4.93对84.43±19.59,P<0.0001)。更重要的是,与早期肝衰竭患者相比,中/晚期患者的MAIT细胞显著减少。疾病改善后,循环MAIT细胞在百分比(4.01±1.21%对2.04±0.95%,P<0.0001)和细胞计数(17.24±8.56对7.41±4.99,P<0.0001)方面均有部分恢复。存活组循环MAIT细胞的比例(2.29±1.01%对1.58±1.38%,P<0.05)和数量(7.30±5.70对2.94±1.47,P<0.001)显著高于死亡/肝移植组,Kaplan-Meier曲线显示循环MAIT细胞低表达(百分比和细胞计数)预示总体生存率较差(P<0.01)。此外,与HCs相比,HBV相关肝衰竭患者的IL-12(20.26±5.42 pg/mL对17.76±2.79 pg/mL,P<0.01)和IL-18(1470.05±1525.38 pg/mL对362.99±109.64 pg/mL,P<0.0001)水平显著升高。

结论

循环MAIT细胞可能在HBV相关肝衰竭过程中起重要作用,可作为重要的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ec/7445862/9b08067aae0c/WJG-26-4703-g001.jpg

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