title: Differential expression of toll-like receptor mRNA in treatment non-responders and sustained virologic responders at baseline in patients with chronic hepatitis C.
abstract: 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.
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Harvard Institutes of Medicine, Boston, MA 02115, USA. qhe@bidmc.harvard.edu
authors.forename: Qi
authors.initials: Q
authors.lastname: He
authors.forename: Camilla S
authors.initials: CS
authors.lastname: Graham
authors.forename: Emanuele
authors.initials: E
authors.lastname: Durante Mangoni
authors.forename: Margaret James
authors.initials: MJ
authors.lastname: Koziel
mesh_terms: 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
chemical_list: 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