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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2016; 22(6): 1966-1974
Published online Feb 14, 2016. doi: 10.3748/wjg.v22.i6.1966
Anti-rods/rings autoantibody generation in hepatitis C patients during interferon-α/ribavirin therapy
Gerson Dierley Keppeke, S John Calise, Edward KL Chan, Luis Eduardo C Andrade
Gerson Dierley Keppeke, Luis Eduardo C Andrade, Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, SP 04023-062, Brazil
S John Calise, Edward KL Chan, Department of Oral Biology, University of Florida, Gainesville, FL 32610-0424, United States
Luis Eduardo C Andrade, Immunology Division, Fleury Medicine and Health Laboratories, São Paulo, SP 04102-050, Brazil
Author contributions: Keppeke GD wrote the original draft; all authors edited and wrote the final version.
Supported by Brazilian government research foundations National Council for Research and Technology and Coordination for the Improvement of Higher Education Personnel with research grant and scholarships process, No. 9028-11-0, No. 305064/2011-8 and No. 232711/2014-3; and by Sao Paulo Government agency Sao Paulo State Research Foundation with process No. 2011/12448-0; both granted to Andrade LEC and Keppeke GD.
Conflict-of-interest statement: The authors declare no commercial or financial conflict of interest to report.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Luis Eduardo C Andrade, Professor, Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatu 740, São Paulo, SP 04023-062, Brazil.
Telephone: +55-11-55764239 Fax: +55-11-55764239
Received: May 12, 2015
Peer-review started: May 15, 2015
First decision: October 14, 2015
Revised: November 4, 2015
Accepted: November 24, 2015
Article in press: November 24, 2015
Published online: February 14, 2016
Core Tip

Core tip: Between 20% and 40% of hepatitis C virus patients treated with interferon-α and ribavirin develop autoantibodies showing a peculiar antinuclear antibodies pattern characterized as rods and rings (RR) structures. In those patients, the first appearance of anti-RR autoantibodies occurs around the sixth month of treatment and reaches a plateau around the twelfth month. The main target of anti-RR autoantibodies is the inosine-5’-monophosphate dehydrogenase 2 (IMPDH2) enzyme, critical in de novo GTP biosynthesis. In cell culture, IMPDH2 inhibition by ribavirin promotes its aggregation into RR structures. These observations led to the hypothesis that anti-RR autoantibody production represents a human model of immunologic tolerance breakdown that allows us to explore interesting aspects of the humoral autoimmune response from the beginning of the putative triggering event.