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慢性丙型肝炎的成功直接抗病毒治疗可降低单核细胞和循环免疫介质中的 HLA-DR:一项长期随访研究。

Successful DAA therapy for chronic hepatitis C reduces HLA-DR on monocytes and circulating immune mediators: A long-term follow-up study.

机构信息

Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Faculdade de Medicina, Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Niterói, RJ, Brazil.

Laboratório de Microbiologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.

出版信息

Immunol Lett. 2020 Dec;228:15-23. doi: 10.1016/j.imlet.2020.09.002. Epub 2020 Sep 15.

Abstract

INTRODUCTION

After DAA treatment for chronic hepatitis C infection, peripheral monocyte subsets from patients who achieved sustained virological response (SVR) reduced compared to healthy control. Improvement in inflammatory parameters and liver stiffness has been observed. However, little is known about the long-term impact of DAA treatment on peripheral monocyte subsets and immune mediators levels.

OBJECTIVES

We aimed to examine peripheral monocyte subsets and immune mediators levels in Brazilian chronic HCV patients after long-term successful IFN-free SOF-based treatment.

MATERIAL AND METHODS

We analyzed CD14++CD16-, CD14++CD16+ and CD14+CD16++ monocytes and 27 immune mediators by flow cytometry and analysis of multiple secreted proteins assay, respectively, in monoinfected chronic HCV patients receiving IFN-free sofosbuvir-based regimens followed before treatment, at SVR and one year after the end of treatment (1y).

RESULTS

Twenty-one biomarkers decreased significantly at 1y and 55-80 % of patients this reduction at 1y. Experimented patients presented a greater modulation of immune mediators at 1y. HLA-DR expression significantly decreased on CD14++CD16- and CD14++CD16+ monocytes at 1y when compared to SVR.

CONCLUSIONS

Successful DAA therapy did not modify monocyte subsets frequency but reduced monocyte activation at 1y and sustained the downregulation and restoration of circulating immune mediators, indicating that long-term reversal of inflammation status could occur after HCV eradication.

摘要

简介

在慢性丙型肝炎感染的直接抗病毒药物 (DAA) 治疗后,与健康对照组相比,获得持续病毒学应答 (SVR) 的患者外周血单核细胞亚群减少。炎症参数和肝硬度的改善已经得到观察。然而,对于 DAA 治疗对外周血单核细胞亚群和免疫介质水平的长期影响知之甚少。

目的

我们旨在研究巴西慢性 HCV 患者在长期成功无干扰素 SOF 为基础的治疗后外周血单核细胞亚群和免疫介质水平。

材料和方法

我们通过流式细胞术分析 CD14++CD16-、CD14++CD16+和 CD14+CD16++单核细胞,通过多重分泌蛋白分析检测 27 种免疫介质,分别分析接受无干扰素 SOF 为基础的方案治疗的慢性 HCV 单感染患者,分别在治疗前、SVR 时和治疗结束后 1 年(1y)时进行分析。

结果

21 种生物标志物在 1y 时显著降低,55-80%的患者在 1y 时降低。实验患者在 1y 时表现出更大的免疫介质调节。与 SVR 相比,CD14++CD16-和 CD14++CD16+单核细胞上 HLA-DR 表达在 1y 时显著降低。

结论

成功的 DAA 治疗并未改变单核细胞亚群的频率,但在 1y 时降低了单核细胞的激活,并持续下调和恢复循环免疫介质,表明 HCV 清除后炎症状态可能长期逆转。

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