Interferon alfa regulated gene expression in patients initiating interferon treatment for chronic hepatitis C

Xuhuai Ji, Ramsey Cheung, Stewart Cooper, Qingqin Li, Harry B. Greenberg, Xiaosong He

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Interferon alfa (IFN-α) is an approved therapeutic agent for chronic hepatitis C. To directly characterize the effects of IFN-α in humans, we used microarrays to profile gene expression in peripheral blood mononuclear cells (PBMCs) from hepatitis C patients treated with IFN-α. Seven patients were studied using two strategies: (1) in vivo: PBMCs were collected immediately before the first dose of IFN-α, and 3 and 6 hours after the dose; (2) ex vivo: PBMCs that were collected before the first IFN-α dose were incubated with IFN-α for 3 and 6 hours. The microarray datasets were analyzed with significance analysis of microarrays (SAM) to identify genes regulated by IFN-α. We identified 516 named genes up-regulated at least 2-fold, at a false discovery rate (FDR) of less than 1%. In vivo and ex vivo studies generated similar results. No genes were identified as regulated differently between these 2 experimental conditions. The up-regulated genes belonged to a broad range of functional pathways and included multiple genes thought to be involved in the direct antiviral effect of IFN-α. Of particular interest, 88 genes directly relating to functions of immune cells were up-regulated, including genes involved in antigen processing and presentation, T-cell activation, lymphocyte trafficking, and effector functions, suggesting that IFN-α up-regulates multiple genes involving different aspects of immune responses to enhance immunity against hepatitis C virus. In conclusion, IFN-α-inducible genes can be identified in human PBMCs in vivo as well as ex vivo. Signature changes associated with diffeferent treatment outcomes may be found among these genes.

Original languageEnglish (US)
Pages (from-to)610-621
Number of pages12
JournalHepatology
Volume37
Issue number3
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

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Chronic Hepatitis C
Interferon-alpha
Interferons
Gene Expression
Genes
Blood Cells
Therapeutics
Antigen Presentation
Microarray Analysis
Hepatitis C
Lymphocyte Activation
Transcriptome
Hepacivirus
Antiviral Agents
Immunity
Up-Regulation
T-Lymphocytes

ASJC Scopus subject areas

  • Hepatology

Cite this

Interferon alfa regulated gene expression in patients initiating interferon treatment for chronic hepatitis C. / Ji, Xuhuai; Cheung, Ramsey; Cooper, Stewart; Li, Qingqin; Greenberg, Harry B.; He, Xiaosong.

In: Hepatology, Vol. 37, No. 3, 01.03.2003, p. 610-621.

Research output: Contribution to journalArticle

Ji, Xuhuai ; Cheung, Ramsey ; Cooper, Stewart ; Li, Qingqin ; Greenberg, Harry B. ; He, Xiaosong. / Interferon alfa regulated gene expression in patients initiating interferon treatment for chronic hepatitis C. In: Hepatology. 2003 ; Vol. 37, No. 3. pp. 610-621.
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