Gene expression signatures of peripheral CD4+ T cells clearly discriminate between patients with acute and chronic hepatitis B infection

Authors

  • Nirupma TrehanPati,

    1. Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
    2. Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany
    3. Division of Cell Biology and Immune Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany
    4. Institute of Liver and Biliary Sciences, New Delhi, India
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    • These authors equally contributed to this work.

  • Robert Geffers,

    1. Division of Cell Biology and Immune Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany
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    • These authors equally contributed to this work.

  • Sukriti,

    1. Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
    2. Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany
    3. Division of Cell Biology and Immune Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany
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  • Syed Hissar,

    1. Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
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  • Peggy Riese,

    1. Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany
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  • Tanja Toepfer,

    1. Division of Cell Biology and Immune Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany
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  • Jan Buer,

    1. Institute of Medical Microbiology, University Hospital Essen, Essen, Germany
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  • Manoj Kumar,

    1. Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
    2. Institute of Liver and Biliary Sciences, New Delhi, India
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  • Carlos A. Guzman,

    1. Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany
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    • C. A. G. and S. K. S. are joint senior authors.

  • Shiv Kumar Sarin

    Corresponding author
    1. Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
    2. Institute of Liver and Biliary Sciences, New Delhi, India
    • Department of Gastroenterology, G.B. Pant Hospital, Institute of Liver and Biliary Sciences, New Delhi, India 110002
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    • C. A. G. and S. K. S. are joint senior authors.

    • fax: (91)-11-23219710.


  • Potential conflict of interest: Nothing to report.

Abstract

CD4+ T and regulatory T cells (Tregs) seem to play a key role in persistence of hepatitis B virus (HBV) infection. However, the molecular events by which Tregs exert their modulatory activity are largely unknown. The transcriptional profiles of CD4+ T cells of healthy controls (HCs) and patients affected by acute hepatitis B (AVH-B) or chronic hepatitis B (CHB) infection were established using a custom expression array consisting of 350 genes relevant for CD4+ T cell and Treg function. These studies were complemented by real-time reverse-transcription polymerase chain reaction. Peripheral blood mononuclear cells (PBMCs) were also analyzed for the presence of Tregs, which were more abundant in the acute stage of the disease (7%) than in HCs and CHB infection (HCs versus AVH-B, P = 0.003; AVH-B versus CHB, P = 0.04). One hundred eighteen genes (34%) intrinsically differentiate HBV-infected patients from HCs. Using gene ontology, we identified T cell receptor signaling and clusterization, mitogen-activated protein kinase kinase signaling, cell adhesion, cytokines and inflammatory responses, cell cycle/cell proliferation, and apoptosis as the most prominent affected modules. A higher expression of CCR1, CCR3, CCR4, CCR5, and CCR8 was seen in AVH-B than in CHB-infected patients and HCs. Annotation of the interconnected functional network of genes provided a unique representation of global immune activation during acute infection. Almost all genes were down-regulated in patients with CHB infection. Conclusion: The fingerprints enable clear discrimination between patients suffering from AVH-B or CHB infection. The observed profiles suggest accumulation of effector T cells with a potential role in necro-inflammation during the acute stage. Subsequent down-regulated effector functions support the hypothesis of suppressed CD4+ effector T cells favoring viral persistence in the chronic infection stage. (HEPATOLOGY 2009.)

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