title: Cytoplasmic rods and rings autoantibodies developed during pegylated interferon and ribavirin therapy in patients with chronic hepatitis C.
abstract: BACKGROUND
  Serum autoantibodies are frequently detected in patients with chronic HCV infection, reflecting the wide spectrum of immune reactions related to this virus. In the present study, a novel autoantibody to cytoplasmic rods and rings (RR) in chronic HCV patients was characterized.
  
  
  METHODS
  Sera from 75 previously untreated HCV patients were investigated by indirect immunofluorescence using HEp-2 cell substrate before and during pegylated interferon (PEG-IFN)/ribavirin (RBV) therapy. HEp-2 cells were cultured and fixed either following standard protocols or with the addition of RBV in culture medium.
  
  
  RESULTS
  In 15 out of 75 (20%) patients, analysis revealed the presence of antibodies to rod-like cytoplasmic structures ranging approximately 3-10 μm in length and rings approximately 2-5 μm in diameter. These RR structures became detectable in >95% of cells after addition of RBV in culture medium, whereas they were absent in untreated cells. Anti-RR antibodies were found in sera collected during PEG-IFN/RBV treatment only, but never detected before antiviral therapy nor in control groups. More importantly, these anti-RR antibodies were more often detected in non-responder/relapsers than in responder patients (33% versus 11%; P-value =0.037).
  
  
  CONCLUSIONS
  An RBV-induced autoantibody was identified to a new cytoplasmic autoantigenic structure developed in HCV patients after PEG-IFN/RBV and this same structure can be induced by RBV in in vitro culture. Owing to the onset of anti-RR antibodies in PEG-IFN/RBV-treated patients and their association with a treatment failure, studies are deemed necessary to clarify whether anti-RR plays a role in the response to PEG-IFN/RBV therapy.
authors.affiliation: Department of Gastroenterology, Istituto Clinico Humanitas, Milan, Italy. giovanni.covini@humanitas.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Covini
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Carcamo
authors.forename: Elena
authors.initials: E
authors.lastname: Bredi
authors.forename: Carlos A
authors.initials: CA
authors.lastname: von Mühlen
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.forename: Edward K L
authors.initials: EK
authors.lastname: Chan
mesh_terms: D000328:Adult; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002460:Cell Line; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015388:Organelles / Q000276:immunology; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D001323:Autoantibodies; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a