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直接作用抗病毒药物(DAAs)对埃及慢性丙型肝炎病毒患者骨髓来源抑制细胞群体的影响:DAAs的潜在免疫调节作用

Effect of Direct Acting Antivirals (DAAs) on Myeloid-Derived Suppressor Cells Population in Egyptian Chronic Hepatitis C Virus Patients: A Potential Immunomodulatory Role of DAAs.

作者信息

Abdulsamad Basma, Afifi Mohamed, Awaad Ashraf K, Elbendary Waleed, Mustafa Hanan, Elsherbini Bassem

机构信息

Immunology and Allergy Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.

Clinical Pharmacist, Ministry of Health, Alexandria, Egypt.

出版信息

Viral Immunol. 2023 May;36(4):259-267. doi: 10.1089/vim.2022.0170. Epub 2023 Feb 20.

Abstract

Chronic hepatitis C is a major health concern with high morbidity and mortality rates. The introduction of direct acting antivirals (DAAs) as a first-line treatment for hepatitis C virus (HCV) has significantly enhanced HCV eradication. However, DAA therapy is facing rising concerns regarding long-term safety, viral resistance, and reinfection. HCV is associated with different immune alteration mechanisms that can evade immunity and establish persistent infection. One of these suggested mechanisms is the accumulation of myeloid-derived suppressor cells (MDSCs), which is known to accumulate in chronic inflammatory conditions. Moreover, the role of DAA in restoring immunity after successful viral eradication is still unclear and needs further investigations. Thus, we aimed to investigate the role of MDSCs in chronic HCV Egyptian patients and its response to DAA in treated compared with untreated patients. Fifty untreated chronic hepatitis C (CHC) patients, 50 DAA-treated CHC patients, and 30 healthy individuals were recruited. We used flow cytometer analysis to measure MDSCs frequency and enzyme-linked immunosorbent assay analysis to evaluate the serum level of interferon (IFN)-. We found a significant elevation in MDSC% among the untreated group (34.5 ± 12.4%) compared with the DAA-treated group (18.3 ± 6.7%), while the control group had a mean of (3.8 ± 1.6%). IFN- concentration was higher in treated patients compared with untreated. We also found a significant negative correlation (rs -0.662) ( < 0.001) between MDSC% and IFN- concentration among treated HCV patients. Our results revealed important evidence of MDSCs accumulation in CHC patients and partial retrieval of the immune system regulatory function after DAA therapy.

摘要

慢性丙型肝炎是一个主要的健康问题,发病率和死亡率都很高。直接作用抗病毒药物(DAAs)作为丙型肝炎病毒(HCV)的一线治疗药物的引入,显著提高了HCV的根除率。然而,DAA治疗在长期安全性、病毒耐药性和再感染方面正面临越来越多的担忧。HCV与不同的免疫改变机制相关,这些机制可以逃避免疫并建立持续感染。其中一种推测的机制是髓源性抑制细胞(MDSCs)的积累,已知其在慢性炎症条件下会积累。此外,DAA在病毒成功根除后恢复免疫的作用仍不清楚,需要进一步研究。因此,我们旨在研究MDSCs在埃及慢性HCV患者中的作用及其与未治疗患者相比对DAA治疗的反应。招募了50名未治疗的慢性丙型肝炎(CHC)患者、50名接受DAA治疗的CHC患者和30名健康个体。我们使用流式细胞仪分析来测量MDSCs频率,并使用酶联免疫吸附测定分析来评估血清干扰素(IFN)-水平。我们发现,与接受DAA治疗的组(18.3±6.7%)相比,未治疗组的MDSC%显著升高(34.5±12.4%),而对照组的平均值为(3.8±1.6%)。治疗患者的IFN-浓度高于未治疗患者。我们还发现,在接受治疗的HCV患者中,MDSC%与IFN-浓度之间存在显著的负相关(rs -0.662)(<0.001)。我们的结果揭示了CHC患者中MDSCs积累的重要证据,以及DAA治疗后免疫系统调节功能的部分恢复。

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