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聚乙二醇化干扰素治疗慢性乙型肝炎患者的RNA测序分析

RNA Sequencing Analysis of Patients with Chronic Hepatitis B Treated Using PEGylated Interferon.

作者信息

Chen Shao-Long, Shen Yao-Jie, Chen Guo-Zhi

机构信息

Department of Infectious Disease Control and Prevention, Yueqing Center for Disease Control and Prevention, Wenzhou, 325600, People's Republic of China.

Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China.

出版信息

Int J Gen Med. 2024 Oct 1;17:4465-4474. doi: 10.2147/IJGM.S474284. eCollection 2024.

DOI:10.2147/IJGM.S474284
PMID:39372134
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11453141/
Abstract

PURPOSE

Worldwide, chronic hepatitis B virus (CHB) infection is a public health concern, ultimately leading to liver cirrhosis and hepatocellular carcinoma. Currently, patients with CHB can be treated using polyethylene glycol (PEG)ylated interferon (PEG-IFN) antiviral therapy, which has both immune modulatory and antiviral properties. This study aimed to reveal the mechanism underlying the effect of PEG-IFN therapy, to rationally optimize this therapeutic option.

PATIENTS AND METHODS

Ten patients with CHB who were positive for the hepatitis B virus e antigen (HBeAg) and were receiving PEG-IFN treatment were enrolled. Clinical and virological parameters were monitored during 48 weeks of treatment. In addition, peripheral blood mononuclear cells (PBMCs) were collected from the 10 patients at 0, 24, and 36 weeks. RNA sequencing technology was used to analyze the RNA expression profile in the PBMC samples.

RESULTS

Following PEG-IFN treatment, we identified 217 differentially expressed genes (DEGs), most of which were upregulated. Gene ontology enrichment analysis of the DEGs revealed that they were enriched in 29 clusters, mainly associated with "antiviral defense", "innate immunity", "immunity", "defense response to virus", "response to virus", "type I interferon signaling pathway", "negative regulation of viral genome replication", "innate immune response", and "RNA-binding".

CONCLUSION

After PEG-IFN treatment, a certain mRNA expression profile was observed in patients with CHB, providing further mechanistic insights into the antiviral effect of this therapy.

摘要

目的

在全球范围内,慢性乙型肝炎病毒(CHB)感染是一个公共卫生问题,最终会导致肝硬化和肝细胞癌。目前,CHB患者可采用聚乙二醇(PEG)化干扰素(PEG-IFN)抗病毒治疗,该治疗具有免疫调节和抗病毒特性。本研究旨在揭示PEG-IFN治疗效果的潜在机制,以合理优化这一治疗方案。

患者与方法

招募了10例乙肝e抗原(HBeAg)阳性且正在接受PEG-IFN治疗的CHB患者。在48周的治疗期间监测临床和病毒学参数。此外,在第0、24和36周从这10例患者中采集外周血单个核细胞(PBMC)。采用RNA测序技术分析PBMC样本中的RNA表达谱。

结果

PEG-IFN治疗后,我们鉴定出217个差异表达基因(DEG),其中大多数呈上调。对DEG进行基因本体富集分析发现,它们富集于29个聚类中,主要与“抗病毒防御”“固有免疫”“免疫”“对病毒的防御反应”“对病毒的反应”“I型干扰素信号通路”“病毒基因组复制的负调控”“固有免疫反应”及“RNA结合”相关。

结论

PEG-IFN治疗后,在CHB患者中观察到一定的mRNA表达谱,为该治疗的抗病毒效果提供了进一步的机制性见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1420/11453141/cabf64d7b1ee/IJGM-17-4465-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1420/11453141/2a3790d85ba1/IJGM-17-4465-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1420/11453141/fbc26e5af37e/IJGM-17-4465-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1420/11453141/7c819a200628/IJGM-17-4465-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1420/11453141/6bdfbab3cb54/IJGM-17-4465-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1420/11453141/cabf64d7b1ee/IJGM-17-4465-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1420/11453141/2a3790d85ba1/IJGM-17-4465-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1420/11453141/fbc26e5af37e/IJGM-17-4465-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1420/11453141/7c819a200628/IJGM-17-4465-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1420/11453141/6bdfbab3cb54/IJGM-17-4465-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1420/11453141/cabf64d7b1ee/IJGM-17-4465-g0005.jpg

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