Skip to main content
SpringerLink
Log in

Autoantibodies against “rods and rings”-related IMPDH2 in hepatitis C genotype 1 and DAA therapy in a “real life” cohort

  • Original Investigation
  • Published:
Medical Microbiology and Immunology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

BCR:

Boceprevir

CHC:

Chronic hepatitis C

DAA:

Direct-acting antivirals

GT 1:

Genotype 1

IFN:

Pegylated interferon

HCV:

Hepatitis C virus

IFA:

Indirect immunofluorescence assay

IMPDH2:

Inosine-5′-monophosphate-dehydrogenase 2

RBV:

Ribavirin

RC-IFA:

Recombinant cell-based indirect immunofluorescence assay

SVR:

Sustained virologic response

TPR:

Telaprevir

References

  1. Seelig HP, Appelhans H, Bauer O, Bluthner M, Hartung K, Schranz P, Schultze D, Seelig CA, Volkmann M (2011) Autoantibodies against inosine-5′-monophosphate dehydrogenase 2–characteristics and prevalence in patients with HCV-infection. Clin Lab 57(9–10):753–765

    CAS  PubMed  Google Scholar 

  2. Probst C, Radzimski C, Blocker IM, Teegen B, Bogdanos DP, Stocker W, Komorowski L (2013) Development of a recombinant cell-based indirect immunofluorescence assay (RC-IFA) for the determination of autoantibodies against “rings and rods”-associated inosine-5′-monophosphate dehydrogenase 2 in viral hepatitis C. Clin Chim Acta 418:91–96. doi:10.1016/j.cca.2013.01.003

    Article  CAS  PubMed  Google Scholar 

  3. Carcamo WC, Ceribelli A, Calise SJ, Krueger C, Liu C, Daves M, Villalta D, Bizzaro N, Satoh M, Chan EK (2013) Differential reactivity to IMPDH2 by anti-rods/rings autoantibodies and unresponsiveness to pegylated interferon-alpha/ribavirin therapy in US and Italian HCV patients. J Clin Immunol 33(2):420–426. doi:10.1007/s10875-012-9827-4

    Article  CAS  PubMed  Google Scholar 

  4. Keppeke GD, Nunes E, Ferraz ML, Silva EA, Granato C, Chan EK, Andrade LE (2012) Longitudinal study of a human drug-induced model of autoantibody to cytoplasmic rods/rings following HCV therapy with ribavirin and interferon-alpha. PLoS ONE 7(9):e45392. doi:10.1371/journal.pone.0045392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Keppeke GD, Prado MS, Nunes E, Perazzio SF, Rodrigues SH, Ferraz ML, Chan EK, Andrade LE (2016) Differential capacity of therapeutic drugs to induce rods/rings structures in vitro and in vivo and generation of anti-rods/rings autoantibodies. Clin Immunol. doi:10.1016/j.clim.2016.10.004

    PubMed  Google Scholar 

  6. Keppeke GD, Satoh M, Ferraz ML, Chan EK, Andrade LE (2014) Temporal evolution of human autoantibody response to cytoplasmic rods and rings structure during anti-HCV therapy with ribavirin and interferon-alpha. Immunol Res 60(1):38–49. doi:10.1007/s12026-014-8515-2

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

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.

Author contributions

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.

Author information

Author notes

  1. Werner Dammermann and Susanne Polywka contributed equally.

Authors and Affiliations

  1. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Werner Dammermann, Malte Wehmeyer, Julian Schulze zur Wiesch & Stefan Lüth

  2. Department of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Susanne Polywka

  3. Institute of Experimental Immunology, EUROIMMUN AG, Seekamp 31, 23560, Lübeck, Germany

    Inga Dettmann, Swantje Mindorf, Lars Komorowski & Winfried Stöcker

  4. University Hospital Brandenburg, Brandenburg Medical School, Center of Internal Medicine II, Hochstrasse 29, 14770, Brandenburg, Germany

    Werner Dammermann & Stefan Lüth

Authors
  1. Werner Dammermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susanne Polywka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Inga Dettmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Swantje Mindorf
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lars Komorowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Malte Wehmeyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Julian Schulze zur Wiesch
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Winfried Stöcker
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Stefan Lüth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Werner Dammermann.

Ethics declarations

Funding

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dammermann, W., Polywka, S., Dettmann, I. et al. Autoantibodies against “rods and rings”-related IMPDH2 in hepatitis C genotype 1 and DAA therapy in a “real life” cohort. Med Microbiol Immunol 206, 379–382 (2017). https://doi.org/10.1007/s00430-017-0516-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00430-017-0516-z

Keywords

Search

Navigation