Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Autoantibodies to miRNA-Binding Protein Argonaute 2 (Su antigen) in Patients with Hepatitis C Virus Infection

Vazquez-Del Mercado1,  Monica, Orozco2,  Laura V. Sánchez, Pauley3,  Brad A., Chan4,  Jason Y.F., Chan4,  Edward K.L., Gonzalez5,  Montserrat Maldonado, Panduro5,  Arturo

Instituto de Investigacion en Reumatologia y del Sistema Musculo Esqueletico, U de G,, Hospital Civil JIM., Guadalajara, Mexico
Instituto de Biología Molecular en Medicina, U de G, Mexico
Dept. of Oral Biology, Univ. of Florida, Gainesville, FL
University of Florida, Gainesville, FL
Hospital Civil FAA, Mexico
Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, U de G, Guadalajara, Mexico
H R 110, IMSS, Mexico
Unidad de Investigación en Epidemiología Clínica, IMSS, Mexico
Dept. of Medicine, Univ. of Florida, Gainesville, FL

Purpose:

Chronic liver diseases caused by hepatitis B (HBV) or C virus (HCV) are common worldwide. In addition to viral infection itself, type I interferon (I-IFN, mainly IFN-alpha), a standard treatment for HCV appears to induce or enhance autoimmunity. Despite reports on autoimmunity in viral hepatitis, studies on lupus-related autoantibodies are limited and inconsistent. Autoantibodies associated with rheumatic diseases were tested in patients with HCV and HBV infection.

Methods:

Ninety Mexican patients (36 male, 54 female, 58 HCV, 6 HCV+HBV, 26 HBV) with chronic viral hepatitis, confirmed by nested- or RT-nested-PCR, HBsAg and anti-HCV antibodies, were studied. Autoantibodies were tested by immunofluorescence, immunoprecipitation (IP), and ELISA.

Results:

Antinuclear antibodies were found in 38% HBV, 17% HBV+HCV, and 28% in HCV. Antimitochondria antibodies (AMA) were found in 10 cases [8 without type I-IFN (I-IFN) therapy, 9 females)]; 12% in HBV, 17% in HBV+HCV, and 10% in HCV. In HCV (and co-infection), all 7 AMA positives were females (17% vs. 0% in males, P= 0.04). Antibodies to a microRNA (miRNA) binding protein Ago2/Su were found in HCV (3/58) or HBV+HCV (1/6) but not in HBV (0/26). Anti-Ago2/Su was in 2/8 HCV treated with I-IFN vs. 2/56 in cases without I-IFN, indicating both anti-Ago2 and AMA can be produced in HCV without I-IFN treatment. HCV did not have other lupus autoantibodies whereas 5/26 of HBV had antiU1RNP+Ku, Ro+La, RNA polymerase II, or U5snRNPs by IP. AMA is more frequent in anti-Ago2/Su positives (3/4) vs. negatives (4/60) (P = 0.0032).

Conclusion:

Lupus autoantibodies were uncommon in HCV except anti-Ago2/Su. HCV and I-IFN have many ways to affect TLR signaling, miRNA and miRNA binding protein Ago2/Su. HCV replication is regulated via miRNA. HCV envelope protein E2 is known to bind to Ago2. To understand the mechanism of specific targeting of Ago2 in HCV may provide insights to specific autoantibody production.

To cite this abstract, please use the following information:
Vazquez-Del Mercado, Monica, Orozco, Laura V. Sánchez, Pauley, Brad A., Chan, Jason Y.F., Chan, Edward K.L., Gonzalez, Montserrat Maldonado, et al; Autoantibodies to miRNA-Binding Protein Argonaute 2 (Su antigen) in Patients with Hepatitis C Virus Infection [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1908
DOI: 10.1002/art.26981

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