title: Temporal association between increased virus-specific Th17 response and spontaneous recovery from recurrent hepatitis C in a liver transplant recipient.
abstract: BACKGROUND
  Spontaneous clearance of hepatitis C virus (HCV) after orthotopic liver transplantation (OLT) is a rare occurrence. Here, we present detailed immunological analysis of an interferon naive OLT recipient receiving uninterrupted immunosuppression who cleared HCV spontaneously 2 years after transplantation.
  
  
  METHODS
  Enzyme-linked immunospot assay analysis of peripheral T-cell interferon gamma (IFN-γ), interleukin (IL)-10, and IL-17 response to HCV core and nonstructural antigen 4 and enzyme-linked immunosorbent assay (ELISA) to collagen (Col) subtypes I, II, IV, and V were performed in the index patient at the time of viral clearance and compared with an OLT cohort with persistent viremia matched for time from OLT, immunosuppression, and histology. Enzyme-linked immunospot assay and ELISA analysis were repeated on the patient 4 years after OLT. Transcription-mediated amplification assays were used to confirm viral clearance.
  
  
  RESULTS
  Compared with a cohort of post-OLT and nontransplanted viremic HCV patients, the index patient with HCV clearance demonstrated higher IL-17, IL-10, and lower IFN-γ response to nonstructural antigen 4 and core antigen and a higher titer of antibodies (Abs) to Col subtypes I, II, and V during clearance. On follow-up 2 years later, HCV-specific IFN-γ was increased in the index patient, with a decline in IL-17 and IL-10 response and Col I, II, and V Ab titer.
  
  
  CONCLUSIONS
  Virus-induced activation of Th-17 cells may contribute to HCV clearance post-OLT. Maintenance of viral suppression may be facilitated by restoration of Th1 (IFN-γ) responses. Modulation of Th17 immunity deserves further attention as a therapeutic strategy in the treatment of HCV recurrence post-OLT.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Anil B
authors.initials: AB
authors.lastname: Seetharam
authors.forename: Brian B
authors.initials: BB
authors.lastname: Borg
authors.forename: Vijay
authors.initials: V
authors.lastname: Subramanian
authors.forename: William C
authors.initials: WC
authors.lastname: Chapman
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Crippin
authors.forename: Thalachallour
authors.initials: T
authors.lastname: Mohanakumar
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000276:immunology / Q000628:therapy; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D008113:Liver Neoplasms / Q000150:complications / Q000276:immunology / Q000628:therapy; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012075:Remission, Spontaneous; D058504:Th17 Cells / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D020381:Interleukin-17; D016753:Interleukin-10; D007371:Interferon-gamma
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