慢性乙型肝炎相关慢加急性肝衰竭前期免疫细胞的表达及意义

王芳; 卢建华; 刘勇钢; 张新羽; 闫会敏

doi:10.3969/j.issn.1001-5256.2023.01.012

慢性乙型肝炎相关慢加急性肝衰竭前期免疫细胞的表达及意义

DOI: 10.3969/j.issn.1001-5256.2023.01.012

王芳^{1, 2},
卢建华²,
刘勇钢³,
张新羽^{1, 2},
闫会敏^{1, 2, , ,}

1.
河北医科大学公共卫生学院流行病学教研室, 石家庄 050017
2.
石家庄市第五医院临床医学研究所, 石家庄 050021
3.
天津市第二人民医院病理科, 天津 300192

基金项目:

天津市第二人民医院重点项目 (YS0016)

伦理学声明：本研究方案于2019年4月30日经由石家庄市第五医院伦理委员会审批，批号：2019009。

利益冲突声明：本研究不存在研究者、伦理委员会成员以及与公开研究成果有关的利益冲突。

作者贡献声明：王芳负责资料分析，撰写论文；卢建华、刘勇钢和张新羽参与课题设计，收集数据；闫会敏负责拟定写作思路，指导撰写文章，修改论文并最后定稿。

详细信息

通信作者:
闫会敏，yanhm2538@163.com (ORCID: 0000-0003-3158-2536)

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出版历程
- 收稿日期: 2022-07-05
- 录用日期: 2022-09-13
- 出版日期: 2023-01-20

Expression and significance of immune cells in patients with hepatitis B virus-related acute-on-chronic pre-liver failure

Fang WANG^{1, 2},
Jianhua LU²,
Yonggang LIU³,
Xinyu ZHANG^{1, 2},
Huimin YAN^{1, 2
, ,
,}

1.
Department of Epidemiology, School of Public Health, Hebei Medical University, Shijiazhuang 050017, China
2.
Clinical Research Center, Shijiazhuang Fifth Hospital, Shijiazhuang 050021, China
3.
Department of Pathology, Tianjin Second People's Hospital, Tianjin 300192, China

Research funding:

Key Project of Tianjin Second People's Hospital (YS0016)

More Information

Corresponding author: YAN Huimin, yanhm2538@163.com (ORCID: 0000-0003-3158-2536)

摘要

摘要: 目的探讨髓系抑制性细胞(MDSC)、调节性T淋巴细胞(Treg)、分泌IL-17的CD4(Th17)和CD8 T淋巴细胞(Tc17)在HBV相关慢加急性肝衰竭前期(pre-ACHBLF)的表达, 为ACHBLF的早期治疗提供思路。方法纳入2018年8月—2019年5月石家庄市第五医院收治的pre-ACHBLF和ACHBLF患者各15例，同时选择慢性乙型肝炎(CHB)患者15例和健康体检者(HC)15例为对照，流式细胞术检测外周血中MDSC、Th17、Treg和Tc17细胞水平，血液分析仪检测血常规并计算中性粒细胞/淋巴细胞比值(NLR)、单核细胞/淋巴细胞比值(MLR)、血小板/淋巴细胞比值(PLR)与全身免疫炎症指数(SIRS)评估患者炎症程度，分析免疫细胞表达与炎症程度的关系。符合正态分布的计量资料多组间比较采用独立样本方差分析，组间进一步两两比较采用LSD-t检验；不服从正态分布的计量资料多组间比较采用Kruskal-Wallis H检验，进一步两两比较采用Nemenyi检验。变量间的相关性采用Pearson线性相关或Spearman秩相关分析。结果与CHB组比较，ACHBLF和pre-ACHBLF组的Th17、Treg和Tc17细胞水平明显升高，同时pre-ACHBLF患者的MDSC细胞水平也明显升高(P值均＜0.05)。相关性分析结果显示，在pre-ACHBLF患者中，MDSC与白细胞数、中性粒细胞数及NLR、MLR、SIRS呈正相关(r值分别为0.775、0.727、0.571、0.786、0.846，P值均＜0.05)，Treg细胞仅与白细胞数呈正相关(r=0.618，P=0.043)，而Th17/Treg值和Tc17细胞水平与淋巴细胞数呈负相关(r值分别为-0.790、-0.795，P值均＜0.05)。结论 pre-ACHBLF患者已存在细胞免疫功能紊乱，MDSC表达与炎症程度密切相关，应早期关注。
- 慢加急性肝功能衰竭 /
- 乙型肝炎, 慢性 /
- T淋巴细胞
Abstract: Objective To investigate the expression of myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), IL-17-producing CD4⁺ T cells (Th17), and CD8⁺ T cells (Tc17) in hepatitis B virus-related acute-on-chronic pre-liver failure (pre-ACHBLF), and to provide ideas for the early treatment of acute-on-chronic hepatitis B liver failure (ACHBLF). Methods A total of patients with pre-ACHBLF and 15 patients with ACHBLF who were hospitalized in Shijiazhuang Fifth Hospital, from August 2018 to May 2019 were enrolled as subjects, and 15 patients with chronic hepatitis B (CHB) and 15 healthy controls (HC) who underwent physical examination were enrolled as controls. Flow cytometry was used to measure the expression levels of MDSC and Th17, Treg, and Tc17 cells in peripheral blood; a blood analyzer was used to measure routine blood parameters and calculate neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index(SIRS) to evaluate the degree of inflammation, and the correlation between the expression of immune cells and the degree of inflammation was analyzed. An analysis of variance for independent samples was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Nemenyi test was used for further comparison between two groups. A Pearson linear correlation analysis or Spearman's rank correlation analysis was used to investigate the correlation between variables. Results Compared with the CHB group, the ACHBLF and pre-ACHBLF groups had significant increases in the expression levels of Th17, Treg, and Tc17 cells, and the pre-ACHBLF group also had a significant increase in the expression level of MDSC (all P < 0.05). The correlation analysis showed that in pre-ACHBLF patients, MDSC were positively correlated with leukocyte count, neutrophil count, NLR, MLR, and SII (r=0.775, 0.727, 0.571, 0.786, and 0.846, all P < 0.05), and Treg cells were only positively correlated with leukocyte count (r=0.618, P=0.043); Th17/Treg ratio and Tc17 cells were negatively correlated with the number of lymphocytes (r=-0.790 and -0.795, both P < 0.05). Conclusion Cellular immune dysfunction is observed in patients with pre-ACHBLF, and the expression of MDSC is closely associated with the degree of inflammation and should be taken seriously in the early stage.
- Acute-on-Chronic Liver Failure /
- Hepatitis B, Chronic /
- T-Lymphocytes

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图 1 四组研究对象MDSC、Th17、Treg和Tc17表达水平

Figure 1. The expression levels of MDSC, Th17, Treg and TC17 in four groups

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表 1 四组研究对象一般特征比较

Table 1. Comparison of general characteristics of four groups

组别	例数	年龄(岁)	性别(男/女，例)	ALT(U/L)	AST(U/L)	HBeAg (+/-)	TBil(μmol/L)	PTA(%)
ACHBLF组	15	45.00±10.86	11/4	67.00(33.00~132.00)¹⁾	88.00(57.70~117.00)¹⁾	10/5¹⁾	279.00(241.00~337.00)¹⁾	38.00(25.00~65.50)²⁾
pre-ACHBLF组	15	48.50±7.47	11/4	57.40(31.20~114.00)¹⁾	54.90(34.00~112.00)¹⁾	10/5¹⁾	76.40(54.70~129.00)¹⁾	43.90(37.50~51.00)²⁾
CHB组	15	43.10±11.72	12/3	57.00(44.00~261.00)¹⁾	46.00(29.00~135.00)¹⁾	12/3¹⁾	20.00(12.00~33.00)¹⁾	84.00(70.50~91.20)
HC组	15	42.10±6.37	12/3	21.10(11.00~32.30)	21.70(17.20~27.90)	0/15	11.60(9.90~14.40)	-
统计值		F=1.326	χ²=0.373	F=18.594	F=27.525	χ²=23.571	F=48.781	F=26.217
P值		0.275	0.946	＜0.001	＜0.001	＜0.001	＜0.001	＜0.001
注：与HC组比较，1)P＜0.05；与CHB组比较，2)P＜0.05。

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表 2 pre-ACHBLF患者免疫细胞水平与炎症指标的关系

Table 2. The relationship between the expression of immune cells and the degree of inflammation in patients with pre-ACHBLF

炎症指标	MDSC		Th17		Treg		Th17/Treg		Tc17
炎症指标	r值	P值	r值	P值	r值	P值	r值	P值	r值	P值
白细胞	0.775	0.001	0.167	0.668	0.618	0.043	-0.286	0.493	-0.533	0.139
中性粒细胞	0.727	0.002	0.250	0.516	0.491	0.125	-0.238	0.570	-0.417	0.265
淋巴细胞	0.079	0.781	-0.611	0.081	0.333	0.318	-0.790	0.020	-0.795	0.010
NLR	0.571	0.026	0.483	0.187	0.255	0.450	0.048	0.911	-0.150	0.700
MLR	0.786	0.001	0.233	0.546	0.236	0.484	0.024	0.955	-0.433	0.244
PLR	0.161	0.567	0.600	0.088	0.018	0.958	0.429	0.289	0.106	0.787
SIRS	0.846	＜0.001	0.233	0.546	0.336	0.312	0.024	0.955	-0.433	0.244

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