1. Ability of peripheral blood mononuclear cells to activate interferon response in vitro is predictive of virological response in HCV patients.
- Author
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Lalle E, Calcaterra S, Horejsh D, Abbate I, D'Offizi G, Abdeddaim A, Vlassi C, Antonucci G, and Capobianchi MR
- Subjects
- Adult, Aged, Apoptosis Regulatory Proteins, Female, Gene Expression Regulation drug effects, Hepatitis C genetics, Humans, Leukocytes, Mononuclear metabolism, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Proteins genetics, Proteins metabolism, RNA-Binding Proteins, Time Factors, Hepatitis C immunology, Hepatitis C virology, Interferon-alpha pharmacology, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear immunology
- 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 IFNalpha + RBV, with pre-therapy frozen PBMC, were retrospectively selected. After a 3 hr PBMC exposure to IFNalpha 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 beta2M 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 IFNalpha +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.
- Published
- 2008