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Differential expression of toll‐like receptor mRNA in treatment non‐responders and sustained virologic responders at baseline in patients with chronic hepatitis C
Author(s) -
He Qi,
Graham Camilla S.,
Mangoni Emanuele Durante,
Koziel Margaret James
Publication year - 2006
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2006.01357.x
Subject(s) - ribavirin , peripheral blood mononuclear cell , immunology , medicine , pegylated interferon , interferon , nfat , tlr2 , toll like receptor , hepatitis c virus , tlr4 , immune system , hepatitis c , virus , biology , innate immune system , transplantation , calcineurin , biochemistry , in vitro
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.