Deiminated Epstein-Barr virus nuclear antigen 1 is a target of anti–citrullinated protein antibodies in rheumatoid arthritis
Article first published online: 28 FEB 2006
Copyright © 2006 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 54, Issue 3, pages 733–741, March 2006
How to Cite
Pratesi, F., Tommasi, C., Anzilotti, C., Chimenti, D. and Migliorini, P. (2006), Deiminated Epstein-Barr virus nuclear antigen 1 is a target of anti–citrullinated protein antibodies in rheumatoid arthritis. Arthritis & Rheumatism, 54: 733–741. doi: 10.1002/art.21629
- Issue published online: 28 FEB 2006
- Article first published online: 28 FEB 2006
- Manuscript Accepted: 7 NOV 2005
- Manuscript Received: 25 JUL 2005
To test the hypothesis that deimination of viral sequences containing Arg–Gly repeats could generate epitopes recognized by anti–citrullinated protein antibodies (ACPAs) that are present in rheumatoid arthritis (RA) sera.
Multiple antigen peptides derived from Epstein-Barr virus (EBV)–encoded Epstein-Barr nuclear antigen 1 (EBNA-1) were synthesized, substituting the arginines with citrulline, and were used to screen RA sera. Anti–cyclic citrullinated peptide antibodies were purified by affinity chromatography and tested on a panel of in vitro deiminated proteins. Their ability to bind in vivo deiminated proteins was evaluated by immunoprecipitation, using EBV-infected cell lines.
Antibodies specific for a peptide corresponding to the EBNA-135–58 sequence containing citrulline in place of arginine (viral citrullinated peptide [VCP]) were detected in 50% of RA sera and in <5% of normal and disease control sera. In addition, affinity-purified anti-VCP antibodies from RA sera reacted with filaggrin-derived citrullinated peptides, with deiminated fibrinogen, and with deiminated recombinant EBNA-1. Moreover, anti-VCP antibodies immunoprecipitated, from the lysate of calcium ionophore–stimulated lymphoblastoid cell lines, an 80-kd band that was reactive with a monoclonal anti–EBNA-1 antibody and with anti–modified citrulline antibodies.
These data indicate that ACPAs react with a viral deiminated protein and suggest that EBV infection may play a role in the induction of these RA-specific antibodies.