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自然杀伤细胞2D受体与B1a细胞在丙型肝炎病毒感染后肝癌和肝硬化中的相互作用

Natural Killer Group 2D Receptor and B1a Cells Crosstalk in Post-Hepatitis C Virus Infection Hepatocellular Carcinoma and Cirrhosis.

作者信息

Hammad Reham, Eldosoky Mona A, Mosaad Alshaimaa M, El-Nasser Asmaa M, Kotb Fatma M, Elshennawy Salwa I, Eldesoky Noha Abdel-Rahman, Selim Mohamed A, Naguib Gina G, Ahmed Ossama A, Alboraie Mohamed, Aglan Reda Badr

机构信息

Clinical Pathology Department, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt.

Hepatogastroenterology and Infectious Diseases Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.

出版信息

J Hepatocell Carcinoma. 2022 Jul 18;9:609-619. doi: 10.2147/JHC.S360886. eCollection 2022.

DOI:10.2147/JHC.S360886
PMID:35879974
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9307915/
Abstract

BACKGROUND

Natural killer (NK) and B1a cells are implicated in innate immune surveillance against chronic hepatitis C virus (CHCV). NK group 2D (NKG2D) receptor is important for B cell differentiation. This study was designed to assess whether B1a cells and NK Cells expressing NKG2D are implicated in post-hepatitis C infection hepatocellular carcinoma (post-HCV HCC) and cirrhosis using flow cytometry and investigate the association between NK-expressing NKG2D and B1a in complications of CHCV infection.

METHODS

In this cross-sectional study, 111 participants were included and divided into the post-HCV HCC (n = 50), post-HCV liver cirrhosis (n = 31), and CHCV (n = 30) groups.

RESULTS

The percentage of B1a cells (B1a%) and the mean fluorescence intensity (MFI) of NKG2D (NKG2D MFI) showed a significant increase in the CHCV group compared with those in the post-HCV liver cirrhosis and post-HCV HCC groups ( < 0.05). A positive correlation was observed between NKG2D MFI and B1a% (r = 0.6, < 0.001). The receiver operating characteristic (ROC) curve revealed that NKG2D MFI and B1a% differentiated between patients with CHCV infection and those with HCC with a sensitivity of 92% and 98%, respectively, and differentiated between patients with CHCV infection and those with liver cirrhosis with a sensitivity of 94% and 90%, respectively.

CONCLUSION

Downregulation of B1a frequency and NKG2D intensity is implicated in the progression of CHCV infection to cirrhosis and HCC. NKG2D receptor is associated with the frequency of circulating B1a cells. NKG2D intensity and B1a% can be used as indicators of CHCV progression.

摘要

背景

自然杀伤(NK)细胞和B1a细胞参与针对慢性丙型肝炎病毒(CHCV)的先天性免疫监视。NK细胞组2D(NKG2D)受体对B细胞分化很重要。本研究旨在使用流式细胞术评估表达NKG2D的B1a细胞和NK细胞是否与丙型肝炎感染后肝细胞癌(HCV感染后HCC)和肝硬化有关,并研究表达NKG2D的NK细胞与B1a细胞在CHCV感染并发症中的关联。

方法

在这项横断面研究中,纳入了111名参与者,并将其分为HCV感染后HCC组(n = 50)、HCV感染后肝硬化组(n = 31)和CHCV组(n = 30)。

结果

与HCV感染后肝硬化组和HCV感染后HCC组相比,CHCV组的B1a细胞百分比(B1a%)和NKG2D的平均荧光强度(NKG2D MFI)显著增加(<0.05)。观察到NKG2D MFI与B1a%之间呈正相关(r = 0.6,<0.001)。受试者工作特征(ROC)曲线显示,NKG2D MFI和B1a%在CHCV感染患者与HCC患者之间进行区分时,敏感性分别为92%和98%;在CHCV感染患者与肝硬化患者之间进行区分时,敏感性分别为94%和90%。

结论

B1a细胞频率和NKG2D强度的下调与CHCV感染进展为肝硬化和HCC有关。NKG2D受体与循环B1a细胞的频率相关。NKG2D强度和B1a%可作为CHCV进展的指标。

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本文引用的文献

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Hepatitis C Virus: Evading the Intracellular Innate Immunity.丙型肝炎病毒:逃避细胞内固有免疫
J Clin Med. 2020 Mar 13;9(3):790. doi: 10.3390/jcm9030790.
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Recent Advances in Molecular Mechanisms of the NKG2D Pathway in Hepatocellular Carcinoma.NKG2D 通路在肝细胞癌中的分子机制的最新进展。
Biomolecules. 2020 Feb 14;10(2):301. doi: 10.3390/biom10020301.
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Loss of NKG2D in murine NK cells leads to increased perforin production upon long-term stimulation with IL-2.在长期接受 IL-2 刺激后,小鼠 NK 细胞中 NKG2D 的缺失会导致穿孔素产生增加。
Eur J Immunol. 2020 Jun;50(6):880-890. doi: 10.1002/eji.201948222. Epub 2020 Feb 20.
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Control of HCV Infection by Natural Killer Cells and Macrophages.自然杀伤细胞和巨噬细胞对 HCV 感染的控制。
Cold Spring Harb Perspect Med. 2020 Sep 1;10(9):a037101. doi: 10.1101/cshperspect.a037101.
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Chronic Hepatitis C: Conspectus of immunological events in the course of fibrosis evolution.慢性丙型肝炎:纤维化演变过程中免疫事件概述。
PLoS One. 2019 Jul 18;14(7):e0219508. doi: 10.1371/journal.pone.0219508. eCollection 2019.
6
Human B-1 Cells and B-1 Cell Antibodies Change With Advancing Age.人类 B-1 细胞和 B-1 细胞抗体随年龄增长而变化。
Front Immunol. 2019 Mar 19;10:483. doi: 10.3389/fimmu.2019.00483. eCollection 2019.
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Landscape of infiltrating B cells and their clinical significance in human hepatocellular carcinoma.人肝细胞癌中浸润性B细胞的图谱及其临床意义
Oncoimmunology. 2019 Feb 7;8(4):e1571388. doi: 10.1080/2162402X.2019.1571388. eCollection 2019.
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The NKG2D axis: an emerging target in cancer immunotherapy.NKG2D 轴:癌症免疫治疗的新兴靶点。
Expert Opin Ther Targets. 2019 Apr;23(4):281-294. doi: 10.1080/14728222.2019.1580693. Epub 2019 Feb 22.
9
Current Status and Perspective Biomarkers in AFP Negative HCC: Towards Screening for and Diagnosing Hepatocellular Carcinoma at an Earlier Stage.甲胎蛋白阴性肝癌的生物标志物现状与展望:迈向早期肝细胞癌的筛查与诊断
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Natural Killer Cells in Liver Disease and Hepatocellular Carcinoma and the NK Cell-Based Immunotherapy.自然杀伤细胞在肝脏疾病和肝细胞癌中的作用及基于 NK 细胞的免疫治疗。
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