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乙肝病毒感染患者免疫细胞线粒体质量改变、线粒体膜电位降低及其与肝脏炎症的相关性

Altered mitochondrial mass and low mitochondrial membrane potential of immune cells in patients with HBV infection and correlation with liver inflammation.

作者信息

Ma Liling, Han Qingzhen, Cheng Longji, Song Huafeng, Qiang Rui, Xu Ping, Gao Fei, Zhu Li, Xu Junchi

机构信息

Department of Clinical Laboratory, The Affiliated Infectious Diseases Hospital of Soochow University, The Fifth People's Hospital of Suzhou, Suzhou, China.

Center of Clinical Laboratory and Translational Medicine, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Suzhou, China.

出版信息

Front Immunol. 2024 Nov 22;15:1477646. doi: 10.3389/fimmu.2024.1477646. eCollection 2024.

Abstract

INTRODUCTION

Mitochondrial membrane potential (MMP) and mitochondrial mass (MM) affect mitochondrial function and lymphocyte activation, but few studies on HBV infection exist. This study aimed to investigate the regulatory mechanism of mitochondrial dysfunction during HBV infection and its clinical significance by analyzing the alterations of MM and MMP in peripheral blood immune cells.

METHODS

The study enrolled 90 participants, including healthy volunteers(HC) and patients with HBV infection, HBV patients were divided into chronic hepatitis B patients (CHB) and liver cirrhosis (LC) according to the study, and CHB was also divided into an inflammation group and a non-inflammation group. Flow cytometry was used to analyze the changes of MM and MMP in peripheral blood immune cells. These analyses were correlated with the presence of CHB and LC and indexes related to liver inflammation.

RESULTS

The study revealed significant variations in the percentage of MMP and MM of CD8T cells associated with the progression of the disease. The MMP percentage of CD8T cells in the LC group exhibited a notable decrease compared to the HC group and CHB groups. Moreover, MMP of CD8T cells demonstrated potential in distinguishing CHB and LC (AUC=0.7341, P=0.0032). Furthermore, in exploring the link between mitochondrial function of immune cells and liver inflammation, the study found a negative correlation between the MMP ratio of CD4T and CD8T cells and AST (p=0.0039 and P=0.0070, r=-0.4405 and r=-0.4146), while the MM of CD8T cells displayed a positive correlation with AST (p=0.0013, r=0.4865). In CHB patients with normal ALT but liver inflammation detected on B-scan ultrasonography, a significant decrease was observed in the MMP percentage of CD8T (66.13 ± 14.27), CD56NK(57.77 ± 17.40) and CD4CD8T (61.98 ± 15.98) cells. Furthermore, it was also found that the percentage of MMP in CD4CD8T cells could serve as an indicator for early liver inflammation and injury (AUC=0.8408, P=0.0052).

DISCUSSION

In this study, we conducted a systematic analysis of the percentage of lymphocyte MMP and MM in various stages of HBV infection. Our findings revealed a correlation between MMP and MM and early liver inflammation, as well as the progression of the infection. This study marked the first demonstration of the clinical diagnostic value of MMP and MM in HBV infection. Furthermore, this was the first study to discuss the mitochondria of lymphocytes and liver inflammation in HBV infection. It enhanced the understanding of the role of T cells in liver inflammation, and elucidated potential markers for the early detection of liver injury and clinical cirrhosis.

摘要

引言

线粒体膜电位(MMP)和线粒体质量(MM)影响线粒体功能和淋巴细胞活化,但关于乙肝病毒(HBV)感染的研究较少。本研究旨在通过分析外周血免疫细胞中MM和MMP的变化,探讨HBV感染期间线粒体功能障碍的调控机制及其临床意义。

方法

本研究纳入90名参与者,包括健康志愿者(HC)和HBV感染患者,根据研究将HBV患者分为慢性乙型肝炎患者(CHB)和肝硬化(LC)患者,CHB又分为炎症组和非炎症组。采用流式细胞术分析外周血免疫细胞中MM和MMP的变化。这些分析与CHB和LC的存在以及与肝脏炎症相关的指标相关。

结果

研究发现,与疾病进展相关的CD8T细胞MMP和MM百分比存在显著差异。与HC组和CHB组相比,LC组CD8T细胞的MMP百分比显著降低。此外,CD8T细胞的MMP在区分CHB和LC方面具有潜力(曲线下面积=0.7341,P=0.0032)。此外,在探索免疫细胞线粒体功能与肝脏炎症之间的联系时,研究发现CD4T和CD8T细胞的MMP比值与谷草转氨酶(AST)呈负相关(p=0.0039和P=0.0070,r=-0.4405和r=-0.4146),而CD8T细胞的MM与AST呈正相关(p=0.0013,r=0.4865)。在谷丙转氨酶(ALT)正常但B超检查发现肝脏有炎症的CHB患者中,CD8T(66.13±14.27)、CD56自然杀伤细胞(NK)(57.77±17.40)和CD4CD8T(61.98±15.98)细胞的MMP百分比显著降低。此外,还发现CD4CD8T细胞中MMP的百分比可作为早期肝脏炎症和损伤的指标(曲线下面积=0.8408,P=0.0052)。

讨论

在本研究中,我们对HBV感染各阶段淋巴细胞MMP和MM的百分比进行了系统分析。我们的研究结果揭示了MMP和MM与早期肝脏炎症以及感染进展之间的相关性。本研究首次证明了MMP和MM在HBV感染中的临床诊断价值。此外,这是第一项讨论HBV感染中淋巴细胞线粒体与肝脏炎症的研究。它加深了对T细胞在肝脏炎症中作用的理解,并阐明了早期检测肝损伤和临床肝硬化的潜在标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38fe/11621101/a2010efe216e/fimmu-15-1477646-g001.jpg

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