Interferon-alpha receptor 1 mRNA expression in peripheral blood mononuclear cells is associated with response to interferon-alpha therapy of patients with chronic hepatitis C

Abstract

Interferon (IFN)-α receptor mRNA expression in liver of patients with chronic hepatitis C has been shown to be a response to IFN-α therapy. The objective of the present study was to determine whether the expression of mRNA for subunit 1 of the IFN-α receptor (IFNAR1) in peripheral blood mononuclear cells (PBMC) is associated with the response to IFN-α in patients with chronic hepatitis C. Thirty patients with positive anti-HCV and HCV-RNA, and abnormal levels of alanine aminotransferase in serum were selected and treated with IFNα2b for one year. Those with HBV or HIV infection, or using alcohol were not included. Thirteen discontinued the treatment and were not evaluated. The IFN-α response was monitored on the basis of alanine aminotransferase level and positivity for HCV-RNA in serum. IFNAR1-mRNA expression in PBMC was measured by reverse transcriptionpolymerase chain reaction before and during the first three months of therapy. The results are reported as IFNAR1-mRNA/ß-actin-mRNA ratio (mean ± SD). Before treatment, responder patients had significantly higher IFNAR1-mRNA expression in PBMC (0.67 ± 0.15; N = 5; P < 0.05) compared to non-responders (0.35 ± 0.17; N = 12) and controls (0.30 ± 0.16; N = 9). Moreover, IFNAR1-mRNA levels were significantly reduced after 3 months of treatment in responders, whereas there were no differences in IFNAR1 expression in nonresponders during IFN-α therapy. Basal IFNAR1-mRNA expression was not correlated with the serum level of alanine and aspartate aminotransferases or the presence of cirrhosis. The present results suggest that IFNAR1-mRNA expression in PBMC is associated with IFN-α response to hepatitis C and may be useful for monitoring therapy in patients with chronic hepatitis C.

Immune response genes receptors expression and polymorphisms in relation to multiple sclerosis susceptibility and response to INF‐β therapy

“…The decrease of cytokine receptors mRNA expression after IFN‐β therapy could be explained by receptors down regulation after interaction of IFN‐β with its receptors , which might be caused by receptor internalization or protein degradation . Moreover, the lower expression in responders than in nonresponders, indicates more interaction of the drug with its receptor in responders .…”

Atorvastatin effects on SREBF1a and SCAP gene expression in mononuclear cells and its relation with lowering-lipids response

“…Peripheral blood mononuclear cells (PBMC) were isolated as previously described [29] and immediately used for RNA extraction. HepG2 cells were used as calibrator for gene expression studies.…”

“…Total RNA was extracted from PMBC and HepG2 cells (1 × 10 6 to 5 × 10 6 ) using TRIzol ® Reagent (Invitrogen-Life Technologies, Carlsbad, CA) as previously described [29]. cDNA was produced from 1 μg of total RNA by Superscript™ II Reverse Transcriptase and SREBF1a and SCAP mRNA were measured by TaqMan real-time PCR assay, using glyceraldehyde-3-phosphate dehydrogenase (GAPD) as reference gene, and mRNA from HepG2 cells was used as calibrator.…”

Quantitative analysis of interferon alpha receptor subunit 1 and suppressor of cytokine signaling 1 gene transcription in blood cells of patients with chronic hepatitis C

“…We and other authors carried out the quantification of ifnar1 in blood cells because it is less invasive and might be correlated with virus clearance in serum, mononuclear cells and probably the liver. Previous studies have analyzed the association of ifnar1 transcription in PBMCs with response to IFN therapy and reduction of serum viral loads using endpoint RT-PCR, but no correlation was found with viral clearance in liver [16,23]. Compared with those studies, our work improves ifnar1 quantification and sensitivity because of the use of real-time RT-PCR.…”