FGL-1/LAG-3 轴与酒精相关性肝炎的病程有关：初步报告

IF 3.3 Q2 GASTROENTEROLOGY & HEPATOLOGY

Journal of Clinical and Experimental Hepatology Pub Date : 2024-10-10 DOI:10.1016/j.jceh.2024.102424

Lasse Pedersen , Lotte L. Eriksen , Frederik H. Brix , Hendrik Vilstrup , Bent Deleuran , Thomas D. Sandahl , Sidsel Støy

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引用次数: 0

摘要

背景酒精相关性肝炎（AH）的短期死亡率高达 40%，这主要与肝细胞再生受损和肝脏炎症失控有关。肝细胞产生的急性期蛋白纤维蛋白原样蛋白 1（FGL-1）通过自分泌信号刺激肝细胞增殖。FGL-1 还是抑制性 T 细胞受体淋巴细胞活化基因 3（LAG-3）的配体。目的我们旨在描述 AH 患者体内 FGL-1 和 LAG-3 的特征，并描述它们与疾病状态和病程的关系。方法32 例 AH 患者在诊断时被纳入，并随访 3 年。我们用 RNA 测序法测定了 FGL-1 和 LAG-3 的肝基因表达，用 ELISA 法测定了血浆中 FGL-1 和可溶性 (s)LAG-3 的表达，用流式细胞术测定了 LAG-3+CD8+ T 细胞的表达。结果确诊为 AH 时，肝脏 FGL-1 mRNA 与 HC 相比有所增加，而血浆 FGL-1 则没有变化。相反，AH 患者肝脏 LAG-3 mRNA 减少。血浆 sLAG-3 水平和 LAG-3+CD8+ T 细胞的频率与 HC 相同。结论我们的数据表明，FGL-1/LAG-3 轴受损可能与 AH 的发病机制和病程有关。

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The FGL-1/LAG-3 Axis is Associated With Disease Course in Alcohol-associated Hepatitis: A Preliminary Report

Background

Alcohol-associated hepatitis (AH) has a short-term mortality rate of up to 40% primarily related to impaired hepatocyte regeneration and uncontrolled liver inflammation. The acute phase protein fibrinogen-like protein 1 (FGL-1) produced by hepatocytes stimulates hepatocyte proliferation by autocrine signaling. FGL-1 also is a ligand for the inhibitory T cell receptor lymphocyte activation gene 3 (LAG-3). In these ways, FGL-1 and LAG-3 have beneficial interactions that could be interrupted in AH.

Aims

We aimed to characterize FGL-1 and LAG-3 in patients with AH and describe their relationship with the disease state and course.

Methods

Thirty-two patients with AH were included at diagnosis and followed up for 3 years. We measured the hepatic gene expression of FGL-1 and LAG-3 using RNA sequencing, plasma FGL-1 and soluble (s)LAG-3 using ELISA, and LAG-3⁺CD8⁺ T cells using flow cytometry. Healthy persons (HC) and patients with stable alcohol-associated cirrhosis served as controls.

Results

At diagnosis of AH, liver FGL-1 mRNA was increased when compared to HC, whereas plasma FGL-1 was unchanged. In contrast, liver LAG-3 mRNA was reduced in AH. Plasma sLAG-3 levels and the frequency of LAG-3⁺CD8⁺ T cells were as in HC. However, those patients who had the lowest plasma FGL-1 and the lowest frequency of LAG-3⁺CD8⁺ T cells at diagnosis had the highest disease severity and mortality.