Longitudinal Study of a Human Drug-Induced Model of Autoantibody to Cytoplasmic Rods/Rings following HCV Therapy with Ribavirin and Interferon-alpha

Author(s)

Keppeke, Gerson Dierley ^[1] ; Nunes, Eunice ^[2] ; Gomes Ferraz, Maria Lucia ^[2] ; Benedito Silva, Eduardo Antonio ^[2] ; Granato, Celso ^{[3, 4]} ; Chan, Edward K. L. ^[5] ; Andrade, Luis Eduardo C. ^{[1, 3]}

Affiliation

^[1] Univ Fed Sao Paulo, Div Rheumatol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Div Gastroenterol, Sao Paulo - Brazil

^[3] Fleury Med & Hlth Labs, Div Immunol, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Div Infect Dis, Sao Paulo - Brazil

^[5] Univ Florida, Dept Oral Biol, Gainesville, FL 32610 - USA

• Document type: Journal article
• Source: PLoS One; v. 7, n. 9 SEP 24 2012.
• Web of Science Citations: 34

Abstract

Background: A novel pattern in the indirect immunofluorescence antinuclear antibody assay on HEp-2 cells (IIF-HEp-2) characterized by cytoplasmic rods and rings (RR) was reported in HCV patients, but stringent disease specificity studies and longitudinal analysis are lacking. We investigated the clinical significance of anti-RR in an HCV cohort with up to a 12-month treatment follow up. Methodology/Results: 597 patients (342 HCV, 55 HCV/HIV, 200 non-HCV) were screened and titered for anti-RR. Serial samples were available from 78 of 176 treated and 27 of 166 untreated patients. Anti-RR was detected in 14.1% of 342 HCV patients, 9.1% of 55 HCV/HIV, 3.4% of 29 Hepatitis B, and none of 171 non-HCV (p<0.0001; HCV versus non-HCV). Anti-RR was present in 38% of 108 patients receiving interferon-alpha/ribavirin, but none in 26 receiving either interferon-alpha or ribavirin, or 166 untreated patients (p<0.0001). Other IIF-HEp-2 patterns were more frequently associated with interferon-alpha treatment alone (52.2%) as compared to interferon-alpha/ribavirin (25%), ribavirin alone (33.3%), and no therapy (26.5%). Anti-RR frequency was not associated with sex, age, ethnicity, HCV genotype or viral load. Anti-RR occurred only after initiation of treatment, beginning as early as 1 month (6%), but by the sixth month >47% tested positive for anti-RR. The anti-RR titer generally increased with sustained treatment and remained high in 53% of patients. After treatment, anti-RR titer was negative in 41%. Non-responders to HCV therapy were 77% in anti-RR-positive versus 64% in anti-RR-negative patients. Response to treatment was not associated with anti-RR titer or the dynamics of anti-RR reactivity during and after treatment. Conclusions: The exquisite association of anti-RR reactivity with combined interferon-a/ribavirin therapy in HCV patients represents a unique model for drug-induced autoantibody generation in humans as demonstrated by the fact that a significant fraction of patients who have anti-RR during therapy becomes anti-RR-negative after completion of therapy. (AU)

• 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