Document Detail


Lack of TGFβ Production by Hepatitis C Virus-Specific T Cells during HCV Acute Phase is Associated with HCV Clearance in HIV co-infection.
MedLine Citation:
PMID:  22326469     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND & AIMS: Immunity and genetic factors govern recovery from acute hepatitis C virus (HCV) infection. No predictive factors have yet been identified in patients coinfected with the human immunodeficiency virus (HIV). We investigated whether early T cell responses to HCV producing transforming-growth-factor beta (TGFβ) 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 analyzed peripheral HCV-specific TGFβ-producing T cells. Patients were genotyped for IL-28B polymorphisms. Healthy donors' 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 TGFβ-producing CD4+ and/or CD8+ T cells were detected in 8/24 (33%) patients. Lack of anti-HCV TGFβ+ cells was characteristic of healthy donors and Group A, except in 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 TGFβ+ cells was associated with persistent viremia in 6/8 cases (p=0.005). This profile remained stable over time. Such TGFβ 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 TGFβ-producing T cells are a new marker independent of the IL-28B gene polymorphism, predicting the lack of spontaneous or therapeutic HCV clearance.
Authors:
Sawsan Harfouch; Marguerite Guiguet; Marc-Antoine Valantin; Assia Samri; Zineb Ouazene; Laurence Slama; Stéphanie Dominguez; Anne Simon; Ioannis Theodorou; Vincent Thibault; Brigitte Autran
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-9
Journal Detail:
Title:  Journal of hepatology     Volume:  -     ISSN:  0168-8278     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
INSERM, UMRS-945, Hôpital Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire F-75013, Paris, France; UPMC Université Paris 06, UMRS-945, Hôpital Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire F-75013, Paris, France.
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