Differential expression of toll-like receptor mRNA in treatment non-responders and sustained virologic responders at baseline in patients with chronic hepatitis C


Qi He, MD, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Rm 216, 330 Brookline Avenue, Boston, MA 02115.
Tel: +617 667 0049
Fax: +617 975 5235
e-mail: qhe@bidmc.harvard.edu


Abstract: Background/Aims: The contribution of the host immune response to sustained virologic response is not clear in patients with chronic hepatitis C (CHC). The aim of this study was to explore the relationship of the toll-like receptor (TLR) expression with the outcome of antiviral therapy in hepatitis C viral infection.

Methods: Peripheral blood mononuclear cells (PBMC) were obtained from 15 CHC patients before a 48-week treatment with pegylated interferon (PEG IFN) α-2a and ribavirin. A multiplex semi-quantitative reverse-trancriptase polymerase chain reaction (RT-PCR) was used to compare the relative abundance of TLR2–9 transcripts.

Results: mRNA levels of TLR2, 3 and 6 were significantly higher in CHC subjects compared with normal controls (n=8). When patients were classified into non-responders (n=8) and sustained virological responders (n=7) according to the virological outcome of the treatment, there was a clear difference in baseline mRNA expression of TLRs and T-helper (Th) 1/2 cytokines. In addition, the mRNA expression of IFN-γ and nuclear factor of activated T cells (NFAT), which is exclusively expressed in activated T cells, was inversely correlated with that of TLR4, 6 and 9 in non-responders.

Conclusions: TLRs mRNA levels are differentially expressed in baseline PBMC of chronic HCV-infected subjects with or without responsiveness to antiviral therapy.