Ability of peripheral blood mononuclear cells to activate interferon response in vitro is predictive of virological response in HCV patients

E. Lalle, S. Calcaterra, D. Horejsh, I. Abbate, G. D'Offizi, A. Abdeddaim, C. Vlassi, G. Antonucci, Maria R. Capobianchi

Research output: Contribution to journalArticle

Abstract

The most reliable predictor of treatment efficacy in hepatitis C is HCV viremia decay at week 12 [early virological response (EVR)]. We investigated whether the ability of peripheral blood mononuclear cells (PBMC) to mount an interferon (IFN) response in vitro could be predictive of EVR. Fifteen patients treated with PEG IFNα+RBV, with pre-therapy frozen PBMC, were retrospectively selected. After a 3 hr PBMC exposure to IFN-α in vitro, up-regulation of mRNA for IFN-stimulated genes (ISG) was measured by membrane super-array. ISG mRNA levels in unstimulated PBMC were low, but β2M and CASP1 were significantly higher in EVR vs non-EVR. ISG mRNA up-regulation by IFN was more pronounced in EVR vs non-EVR. For 7 genes (IP-10, IFIT1, IFIT2, IFIT3, TRAIL, KIAA1628 and OAS2) cut-off levels were established, by ROC analysis, able to correctly classify all EVR and non-EVR. Early virological response to PEG-IFNα+RBV is correlated with the pre-therapy ability of PBMC to activate an IFN response in vitro. If validated in a wider cohort of patients, the ability of this set of ISG to discriminate between EVR and non-EVR may be useful for pre-therapy evaluation, particularly in patients with unfavourable combinations of conventional response predictors.

Original languageEnglish
Pages (from-to)153-160
Number of pages8
JournalJournal of Biological Regulators and Homeostatic Agents
Volume22
Issue number3
Publication statusPublished - Jul 2008

Keywords

  • Early virological response
  • HCV
  • Interferon response genes
  • Predictor
  • Super-array

ASJC Scopus subject areas

  • Cancer Research
  • Endocrinology
  • Physiology
  • Immunology
  • Endocrinology, Diabetes and Metabolism
  • Immunology and Allergy
  • Oncology
  • Physiology (medical)

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