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Anti-rods/rings autoantibody generation in hepatitis C patients during interferon-α/ribavirin therapy.
- Source :
-
World journal of gastroenterology [World J Gastroenterol] 2016 Feb 14; Vol. 22 (6), pp. 1966-74. - Publication Year :
- 2016
-
Abstract
- Chronic inflammation associated with hepatitis C virus (HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α (IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies (ANA). Between 20% to 40% of HCV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings (RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings (anti-RR) autoantibody production by HCV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2 (IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon.
- Subjects :
- Drug Therapy, Combination
Hepatitis C, Chronic diagnosis
Hepatitis C, Chronic immunology
Humans
IMP Dehydrogenase antagonists & inhibitors
IMP Dehydrogenase chemistry
Immunity, Humoral drug effects
Protein Conformation
Self Tolerance drug effects
Time Factors
Treatment Outcome
Antibodies, Antinuclear immunology
Antiviral Agents adverse effects
Autoimmunity drug effects
Hepatitis C, Chronic drug therapy
IMP Dehydrogenase immunology
Interferon-alpha adverse effects
Ribavirin adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 2219-2840
- Volume :
- 22
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- World journal of gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 26877604
- Full Text :
- https://doi.org/10.3748/wjg.v22.i6.1966