Cytoplasmic rods and rings autoantibodies developed during pegylated interferon and ribavirin therapy in patients with chronic hepatitis C

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 mu m in length and rings approximately 2-5 mu m 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.