Autoantibodies to a miRNA-binding protein Argonaute2 (Su antigen) in patients with hepatitis C virus infection.
OBJECTIVE
Chronic liver diseases caused by hepatitis B (HBV) or C virus (HCV) are common worldwide. Despite reports on autoimmunity in viral hepatitis, studies on autoantibodies associated with systemic rheumatic diseases are inconsistent. Testing of a small number of selected autoantibody specificities using ELISA appears to be one reason for inconsistency. Sera from patients with viral hepatitis were tested by immunoprecipitation that will allow unbiased screening of autoantibodies found in systemic rheumatic diseases.


METHODS
Ninety Mexican patients (37 male, 53 female, 26 HBV, 6 HBV+HCV, 58 HCV) with chronic viral hepatitis, confirmed by nested or RT-nested-PCR, HBsAg and anti-HCV antibodies, were studied. Autoantibodies were tested by immunofluorescence, immunoprecipitation and ELISA. Specificities were verified using reference sera.


RESULTS
Antinuclear antibodies were found in 38% HBV, 17% HBV+HCV, and 28% in HCV. Autoantibodies to Argonaute (Ago2, Su antigen), a microRNA binding protein that plays a key role in RNA-induced silencing complex (RISC), was found in 5% (4/64) of HCV or HBV+HCV coinfected patients but not in HBV (0/26). Anti-Ago2/Su was found in 1/2 of I-IFN-treated case vs. 3/62 in cases without I-IFN. HCV did not have other lupus autoantibodies whereas 19% (5/26) of HBV had anti-U1RNP+Ku, Ro+La, RNA polymerase II, or possible U5snRNPs.


CONCLUSIONS
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. To understand the mechanism of specific targeting of Ago2 in HCV may provide a clue to understand the mechanism of specific autoantibody production.
Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético (IIRSME), Universidad de Guadalajara, Mexico. dravme@hotmail.com
M
M
Vázquez-Del Mercado
L V
LV
Sánchez-Orozco
B A
BA
Pauley
J Y F
JY
Chan
E K L
EK
Chan
A
A
Panduro
M
M
Maldonado González
M A
MA
Jiménez-Luévanos
B T
BT
Martín-Márquez
C A
CA
Palafox-Sánchez
I P
IP
Dávalos-Rodríguez
M
M
Salazar-Páramo
L
L
González-López
J I
JI
Gámez-Nava
M
M
Satoh
D000293:Adolescent; D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D060565:Argonaute Proteins; D001323:Autoantibodies / Q000276:immunology*; D002648:Child; D015852:Eukaryotic Initiation Factor-2 / Q000276:immunology*; D005260:Female; D016174:Hepacivirus / Q000276:immunology / Q000502:physiology; D006509:Hepatitis B / Q000097:blood / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006526:Hepatitis C / Q000097:blood / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D007370:Interferon Type I / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D051193:Toll-Like Receptors / Q000378:metabolism; D055815:Young Adult
C466422:AGO2 protein, human; D060565:Argonaute Proteins; D001323:Autoantibodies; D015852:Eukaryotic Initiation Factor-2; D006514:Hepatitis B Surface Antigens; D018937:Hepatitis C Antibodies; D007370:Interferon Type I; D035683:MicroRNAs; D051193:Toll-Like Receptors