Ability of peripheral blood mononuclear cells to activate interferon response in vitro is predictive of virological response in HCV patients.
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.
Lalle
E
E
Laboratory of Virology, National Institute for Infectious Diseases (INMI) L. Spallanzani, Rome, Italy.
Calcaterra
S
S
Horejsh
D
D
Abbate
I
I
D'Offizi
G
G
Abdeddaim
A
A
Vlassi
C
C
Antonucci
G
G
Capobianchi
M R
MR
D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D013997:Time Factors
D051017:Apoptosis Regulatory Proteins; C484289:IFIT2 protein, human; D016898:Interferon-alpha; D011506:Proteins; D016601:RNA-Binding Proteins