Temporal evolution of human autoantibody response to cytoplasmic rods and rings structure during anti-HCV therapy with ribavirin and interferon-alpha

Temporal evolution of human autoantibody response to cytoplasmic rods and rings structure during anti-HCV therapy with ribavirin and interferon-alpha

Author Keppeke, Gerson Dierley Autor UNIFESP Google Scholar
Satoh, Minoru Google Scholar
Gomes Ferraz, Maria Lucia Autor UNIFESP Google Scholar
Chan, Edward K. L. Google Scholar
Andrade, Luis Eduardo C. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Florida
Univ Occupat & Environm Hlth
Fleury Med & Hlth Labs
Abstract Autoantibodies to inosine monophosphate dehydrogenase-2 (IMPDH2), an enzyme involved in de novo biosynthesis of guanine nucleotides, are observed in a subset of hepatitis C virus (HCV) patients receiving interferon alpha (IFN-alpha) plus ribavirin. Anti-IMPDH2 antibodies display a peculiar cytoplasmic rod/ring (RR) pattern in IIF-HEp-2. We examined the dynamics of anti-RR autoimmune response with respect to immunoglobulin isotypes, titer, avidity, and protein targets in 80 sequential samples from 15 HCV patients (plus 12 randomly selected anti-RR-positive, totalizing 92 samples) collected over an 18-month period, including samples collected before, during, and after IFN-alpha + ribavirin treatment. Immunoprecipitation showed reactivity with the 55 kDa IMPDH2 protein in 12/15 patients (80 %) and 11/15 (73 %) reacted with IMPDH2 in a sandwich ELISA. During treatment, anti-IMPDH2 autoantibodies hit their highest levels after 6-12 months of treatment and decreased post-treatment, while anti-HCV antibodies levels were stable over time. Anti-IMPDH2 IgM levels increased up until the sixth month of treatment and remained stable thereafter, while IgG levels increased steadily up to the twelfth month. Both IgG and IgM decreased during the post-treatment period. IgG avidity increased steadily up to the twelfth month of treatment. in conclusion, this study showed that the temporal kinetics of IFN-alpha + ribavirin-induced humoral autoimmune response to IMPDH2 exhibited a considerably delayed pace of increase in antibody levels and avidity as well as in isotype class switch in comparison with a conventional humoral response to infectious agents. These unique findings uncover intriguing differences between the autoimmune response and the immune response to exogenous agents in humans.
Keywords Autoantibodies
IMPDH2
Hepatitis C
Ribavirin
Interferon-alpha
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2010/50710-6
FAPESP: 2011/12448-0
CAPES: 9028-11-0
CNPq: 305064/2011-8
Date 2014-10-01
Published in Immunologic Research. Totowa: Humana Press Inc, v. 60, n. 1, p. 38-49, 2014.
ISSN 0257-277X (Sherpa/Romeo, impact factor)
Publisher Humana Press Inc
Extent 38-49
Origin http://dx.doi.org/10.1007/s12026-014-8515-2
Access rights Closed access
Type Article
Web of Science ID WOS:000341915800006
URI http://repositorio.unifesp.br/handle/11600/38274

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