Autoantibodies against “rods and rings”-related IMPDH2 in hepatitis C genotype 1 and DAA therapy in a “real life” cohort
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Autoantibodies against inosine-5′-monophosphate-dehydrogenase-2 (IMPDH2; “rods and rings” pattern) develop in chronic hepatitis C (CHC) patients under treatment with peg-interferon (IFN) and ribavirin (RBV), an inhibitor of IMPDH2. We investigated the influence of the alternative therapy with direct-acting antivirals (DAA)/ribavirin on anti-IMPDH2 autoantibody generation and the use of anti-IMPDH2 development as a marker for therapy outcome (sustained virologic response, SVR). We analyzed a “real life” cohort of 104 unselected CHC genotype 1 (GT1) patients treated with IFN/first-generation DAA/RBV prospectively compared to a historic cohort of 59 IFN/RBV-treated CHC GT1 patients. First-generation DAA were boceprevir (BOC) or telaprevir (TPR). Serum autoantibodies were tested by indirect immunofluorescence (IFA) using recombinant IMPDH2 expressing HEK293 cells and native HEp2-cells as substrates. 64/163 (39%) CHC patients turned anti-IMPDH2 positive during therapy, but only 43/163 (26%) showed also “rods and rings” structures. 99/163 (61%) were tested as anti-IMPDH2 negative. 53/104 (51%) CHC patients undergoing IFN/DAA/RBV therapy were anti-IMPDH2 positive and 38/104 (37%) were in parallel anti-“rods and rings” positive. HCV clearance/SVR rate after IFN/DAA/RBV therapy and anti-IMPDH2 status were not significantly dependent. CHC GT1 patients treated with IFN/first-generation DAA/RBV developed anti-IMPDH2 autoantibodies comparable to previous studies including patients under IFN/RBV therapy. Anti-IMPDH2 titers show no use as a marker for therapy outcome in CHC GT1 patients.
KeywordsAutoantibodies Hepatitis C Sustained virologic response Direct-acting antivirals
Chronic hepatitis C
- GT 1
Hepatitis C virus
Indirect immunofluorescence assay
Recombinant cell-based indirect immunofluorescence assay
Sustained virologic response
We thank the donors who participated in this study. We also thank Katharina Heinzel (1. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany) for the excellent technical assistance.
WD, SP and LK developed the study concept and design. ID and SM acquired and analyzed the data. WD drafted the manuscript. WS and SL provided critical revision of the manuscript for important intellectual content. WD conducted the statistical analysis. SP, MW and JSzW provided essential administrative and material support. SL was the study supervisor.
Compliance with ethical standards
This study was not specifically funded by any institution
Conflict of interests
WS discloses stock ownership/equity and directorship for EUROIMMUN AG. ID, SM and LK disclose employment for EUROIMMUN AG. All other authors declare no conflict of interest.
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