Z Gastroenterol 2016; 54(12): 1343-1404
DOI: 10.1055/s-0036-1597391
2. Clinical Hepatology
Georg Thieme Verlag KG Stuttgart · New York

Development of autoantibodies against “rings and rods”-associated IMPDH2 in chronic hepatitis C genotype 1 infection during protease inhibitor based triple therapy in a “real life” cohort

W Dammermann
1   Brandenburg Medical School, Center of Internal Medicine II, Brandenburg an der Havel, Germany
,
S Polywka
3   University Medical Center Hamburg-Eppendorf, Department of Medical Microbiology, Virology and Hygiene, Hamburg, Germany
,
I Dettmann
4   Euroimmun AG, Institute of Experimental Immunology, Lübeck, Germany
,
S Mindorf
4   Euroimmun AG, Institute of Experimental Immunology, Lübeck, Germany
,
L Komorowski
4   Euroimmun AG, Institute of Experimental Immunology, Lübeck, Germany
,
M Wehmeyer
2   University Medical Center Hamburg-Eppendorf, 1. Department of Medicine, Hamburg, Germany
,
J Schulze zur Wiesch
2   University Medical Center Hamburg-Eppendorf, 1. Department of Medicine, Hamburg, Germany
,
W Stöcker
4   Euroimmun AG, Institute of Experimental Immunology, Lübeck, Germany
,
S Lüth
1   Brandenburg Medical School, Center of Internal Medicine II, Brandenburg an der Havel, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
19 December 2016 (online)

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Background: Autoantibodies against inosine-5′-monophosphate dehydrogenase 2 (IMPDH2; “rings and rods” 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 a regimen including 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).

Patients and methods: We analyzed a “real life” cohort of 104 unselected CHC genotype 1 (GT1) patients treated with IFN/1st-generation DAA/RBV prospectively compared to a historic cohort of 59 IFN/RBV treated CHC GT1 patients. 1st-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.

Results: 64/163 (39%) CHC patients turned anti-IMPDH2 positive during therapy, but only 43/163 (26%) showed also “rings and rods” structures. 99/163 (61%) were tested 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-“rings and rods” positive. HCV clearance/SVR rate after IFN/DAA/RBV therapy and anti-IMPDH2 status were not significantly correlated.

Conclusion: CHC GT1 patients treated with IFN/1st-generation DAA/RBV developed anti-IMPDH2 autoantibodies comparable to previous studies including patients under IFN/RBV therapy. Anti-IMPDH2 development promises no use as a marker for therapy outcome in CHC GT1 patients.