HCV-related liver and lymphoproliferative diseases: Association with polymorphisms of IL28B and TLR2

Valli de Re, Mariangela De Zorzi, Laura Caggiari, Gianfranco Lauletta, Maria Lina Tornesello, Elisa Fognani, Marta Miorin, Vito Racanelli, Luca Quartuccio, Laura Gragnani, Sabino Russi, Fabio Pavone, Michela Ghersetti, Elena Garlatti Costa, Pietro Casarin, Riccardo Bomben, Cesare Mazzaro, Giancarlo Basaglia, Massimiliano Berretta, Emanuela VaccherFrancesco Izzo, Franco Maria Buonaguro, Salvatore de Vita, Anna Linda Zignego, Paolo D. de Paoli, Riccardo Dolcetti

Research output: Contribution to journalArticle

Abstract

To explore the relationship between innate immunity and hepatitis C Virus (HCV) in determining the risk of cirrhosis (CIR), hepatocellular carcinoma (HCC), mixed cryoglobulinemia syndrome (MCS) and non-Hodgkin lymphoma (NHL), we investigated the impact of the toll-like receptor-2 (TLR2) and interleukin-28B (IL28B) genetic variants. TLR2 -174 del variant was associated with TLR2 expression and with specific downstream molecules that drive the expression of different interleukins; rs12979860 Il28B was important in response to interferon-treatment and in spontaneous clearance of HCV. The risk for liver and lymphoproliferative diseases in HCV progression was clarified by stratifying 862 HCV-positive patients into groups based on liver (CIR, HCC) and lymphoproliferative HCV-related diseases (MCS, NHL) and compared with chronic HCV (CHC) infection. Analysis of TLR2-IL28B haplotypes showed an association of wild type haplotype with the lymphoproliferative diseases (OR 1.77, p = 0.029) and a slight increase in HCV viral load (HR 1.38, p = 0.054). Wild type haplotype (TLR2 ins/ins- IL28B C/C) was also found associated with older age in patients with an hepatic diseases (in CIR and in HCC p = 0.038 and p = 0.020, respectively) supporting an effect of innate immunity in the liver disease progression. TLR2 and IL28B polymorphisms in combination showed a role in the control of HCV viral load and different HCV disease progression.

Original languageEnglish
Pages (from-to)37487-37497
Number of pages11
JournalOncotarget
Volume7
Issue number25
DOIs
Publication statusPublished - 2016

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Keywords

  • HCC
  • HCV
  • IL28B
  • Immune response
  • Immunity
  • Immunology and Microbiology Section
  • NHL
  • TLR2

ASJC Scopus subject areas

  • Oncology

Cite this

de Re, V., De Zorzi, M., Caggiari, L., Lauletta, G., Tornesello, M. L., Fognani, E., Miorin, M., Racanelli, V., Quartuccio, L., Gragnani, L., Russi, S., Pavone, F., Ghersetti, M., Costa, E. G., Casarin, P., Bomben, R., Mazzaro, C., Basaglia, G., Berretta, M., ... Dolcetti, R. (2016). HCV-related liver and lymphoproliferative diseases: Association with polymorphisms of IL28B and TLR2. Oncotarget, 7(25), 37487-37497. https://doi.org/10.18632/oncotarget.9303