Differential expression of toll-like receptor mRNA in treatment non-responders and sustained virologic responders at baseline in patients with chronic hepatitis C.
OBJECTIVE
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) alpha-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-gamma 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.
He
Qi
Q
Beth Israel Deaconess Medical Center, Harvard Medical School, Harvard Institutes of Medicine, Boston, MA 02115, USA. qhe@bidmc.harvard.edu
Graham
Camilla S
CS
Durante Mangoni
Emanuele
E
Koziel
Margaret James
MJ
D000998:Antiviral Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007371:Interferon-gamma / Q000235:genetics; D008297:Male; D008875:Middle Aged; D050778:NFATC Transcription Factors / Q000235:genetics; D011092:Polyethylene Glycols / Q000627:therapeutic use; D012333:RNA, Messenger / Q000097:blood*; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012254:Ribavirin / Q000627:therapeutic use; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics*; D016896:Treatment Outcome
D000998:Antiviral Agents; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D050778:NFATC Transcription Factors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D051193:Toll-Like Receptors; D011092:Polyethylene Glycols; D012254:Ribavirin; D007371:Interferon-gamma; C100416:peginterferon alfa-2a