Lack of TGF-尾 production by hepatitis C virus-specific T cells during HCV acute phase is associated with HCV clearance in HIV coinfection

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• 作者：Sawsan Harfouch¹ ; ² ; Marguerite Guiguet³ ; ⁴ ; Marc-Antoine Valantin³ ; ⁵ ; Assia Samri¹ ; ² ; ⁶ ; Zineb Ouazene⁷ ; Laurence Slama⁸ ; Sté ; phanie Dominguez⁹ ; Anne Simon¹⁰ ; Ioannis Theodorou¹ ; ² ; ¹¹ ; Vincent Thibault¹² ; Brigitte Autran¹ ; ² ; ¹¹ ; ^{brigitte.autran@psl.aphp.fr} ; The ANRS HC EP21 study group
• 关键词：TGF-尾 ; transforming growth factor-beta ; HCV ; hepatitis C virus ; HIV ; human immunodeficiency virus ; ICS ; intracellular cytokine staining ; IFN ; interferon ; SVR ; sustained virologic response ; RVR ; rapid virologic response ; PBMC ; peripheral blood mononuclear
• 刊名：Journal of Hepatology
• 出版年：2012
• 期刊代码：162_01688278
• 类别：med
• 出版时间：June, 2012
• 卷：56
• 期：6
• 页码：1259-1268
• 文件大小：1256 K

摘要

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Background & Aims

Immunity and genetic factors govern the recovery from acute hepatitis C virus (HCV) infection. No predictive factors have been yet identified in patients coinfected with the human immunodeficiency virus (HIV). We investigated whether early T cell responses to HCV producing transforming-growth-factor beta (TGF-尾) predict the outcome of acute HCV coinfection, independently of the IL-28B gene polymorphism.

Methods

Intracellular cytokine staining assays against HCV-core, E1, NS2, and NS4 overlapping peptides were used for the analysis of peripheral HCV-specific TGF-尾-producing T cells. Patients were genotyped for IL-28B polymorphisms. Healthy donors鈥?samples were tested as controls. Twenty-four acute hepatitis C-HIV+ patients were followed-up for 15 months defining two groups: (A) Recovered (n = 16, 5 spontaneous recoveries, 11 sustained virologic response after treatment), (B) Chronic HCV (n = 8, 4 spontaneous chronic course, 4 therapeutic failures).

Results

During the acute pretreatment phase, core/NS2-specific TGF-尾-producing CD4+ and/or CD8+ T cells were detected in 8/24 (33%) patients. Lack of anti-HCV TGF-尾+ cells was characteristic of healthy donors and Group A, except for 2 cases, with frequencies significantly lower than in Group B (p = 0.04 and 0.01), and was associated with recovery in 14/16 cases. Presence of anti-HCV TGF-尾+ cells was associated with persistent viremia in 6/8 cases (p = 0.005). This profile remained stable over time. Such TGF-尾 production was independent of the rs129679860 SNP (p = 1.0) which was not associated with recovery (p = 1.0).

Conclusions

During acute hepatitis C, pre-therapeutic HCV-specific TGF-尾-producing T cells are a new marker independent of the IL-28B gene polymorphism, predicting the lack of spontaneous or therapeutic HCV clearance.