TIM-3和LAG-3在酒精性肝病中与细胞因子和趋化因子的作用及相关性

Roles and correlations of TIM-3 and LAG-3 with cytokines and chemokines in alcoholic liver disease.

作者信息

Fadriquela Ailyn, Kim Cheol-Su, Lee Jong-Han

机构信息

Department of Laboratory Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea; Department of Convergence Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.

Department of Convergence Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.

出版信息

Clin Chim Acta. 2023 Feb 15;541:117248. doi: 10.1016/j.cca.2023.117248. Epub 2023 Feb 9.

DOI:10.1016/j.cca.2023.117248

PMID:36764507

Abstract

BACKGROUND

Dysregulation of immune checkpoint regulators has been reported in alcoholic liver disease (ALD). This study was designed to assess the serum levels of cytokines and chemokines associated with ALD and uncover the possible disease correlations with the soluble TIM-3 and LAG-3.

METHODS

The soluble TIM-3 and LAG-3 levels were measured by enzyme-linked immunoassay, and 14 cytokines and chemokines were measured using Luminex-based multiplex assay in 111 male ALD patients and 45 healthy controls (HCs).

RESULTS

Our results showed that soluble TIM-3 was significantly increased (p < 0.001) while soluble LAG-3 was significantly decreased (p < 0.001) in ALD group compared to HCs. Among the 14 cytokines and chemokines assessed, granulocyte-colony stimulating factor (G-CSF) (p = 0.003) and interferon γ-induced protein (IP)-10 (p < 0.001) were significantly increased, while interleukin (IL)-4 (p = 0.005) and IL-12 (p40) (p = 0.001) were significantly decreased in the ALD group. Kaplan-Meier analysis showed that overall survival decreased in higher TIM-3 level individuals.

CONCLUSIONS

Our results showed that TIM-3, LAG-3, and IP-10 appear to be important for clinical diagnosis of ALD and ALD severity and may represent potential therapeutic targets in ALD.

摘要

背景

已有报道称免疫检查点调节因子在酒精性肝病（ALD）中存在失调。本研究旨在评估与ALD相关的细胞因子和趋化因子的血清水平，并揭示可溶性TIM-3和LAG-3与该疾病可能存在的关联。

方法

采用酶联免疫吸附测定法测量可溶性TIM-3和LAG-3水平，并使用基于Luminex的多重检测法在111例男性ALD患者和45例健康对照者（HCs）中检测14种细胞因子和趋化因子。

结果

我们的结果显示，与HCs相比，ALD组中可溶性TIM-3显著升高（p < 0.001），而可溶性LAG-3显著降低（p < 0.001）。在评估的14种细胞因子和趋化因子中，粒细胞集落刺激因子（G-CSF）（p = 0.003）和干扰素γ诱导蛋白（IP）-10（p < 0.001）显著升高，而白细胞介素（IL）-4（p = 0.005）和IL-12（p40）（p = 0.001）在ALD组中显著降低。Kaplan-Meier分析显示，TIM-3水平较高的个体总体生存率降低。