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

Author(s)

Keppeke, Gerson Dierley ^{[1, 2]} ; Satoh, Minoru ^{[3, 4]} ; Gomes Ferraz, Maria Lucia ^[5] ; Chan, Edward K. L. ^[1] ; Andrade, Luis Eduardo C. ^{[2, 6]}

Affiliation

^[1] Univ Florida, Dept Oral Biol, Gainesville, FL 32610 - USA

^[2] Univ Fed Sao Paulo, Div Rheumatol, BR-04023062 Sao Paulo - Brazil

^[3] Univ Occupat & Environm Hlth, Sch Hlth Sci, Dept Clin Nursing, Yahata Nishi Ku, Kitakyushu, Fukuoka 8078555 - Japan

^[4] Univ Florida, Dept Med, Div Rheumatol & Clin Immunol, Gainesville, FL 32610 - USA

^[5] Univ Fed Sao Paulo, Div Gastroenterol, BR-04023062 Sao Paulo - Brazil

^[6] Fleury Med & Hlth Labs, Div Immunol, BR-04102050 Sao Paulo - Brazil

• Document type: Journal article
• Source: IMMUNOLOGIC RESEARCH; v. 60, n. 1, p. 38-49, OCT 2014.
• Web of Science Citations: 15

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. (AU)

• FAPESP's process: 11/12448-0 - Antibodies anti-"Rods & Rings", HCV and ribavirin/interferon: A human model of autoantibodies generation.
• Grantee: Gerson Dierley Keppeke
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/50710-6 - Characterization of PF-IV and R&R immunofluorescence patterns observed in the ANA-HEp-2 assay
• Grantee: Luiz Eduardo Coelho Andrade
• Support Opportunities: Regular Research Grants