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Open Access Highly Accessed Research article

Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin

Erik R Vossenaar1*, Normand Després2, Elvy Lapointe2, Annemarie van der Heijden1, Maximillian Lora2, Tatsuo Senshu3, Walther J van Venrooij1 and Henri A Ménard2

Author Affiliations

1 Department of Biochemistry, University of Nijmegen, Nijmegen, The Netherlands

2 Division of Rheumatology, McGill University Health Centre, Montreal, Canada

3 Graduate School of Integrated Science, Yokohama City University, Yokohama, Japan

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Arthritis Res Ther 2004, 6:R142-R150  doi:10.1186/ar1149

Published: 5 February 2004

Abstract

Antibodies directed to the Sa antigen are highly specific for rheumatoid arthritis (RA) and can be detected in approximately 40% of RA sera. The antigen, a doublet of protein bands of about 50 kDa, is present in placenta and in RA synovial tissue. Although it has been stated that the Sa antigen is citrullinated vimentin, experimental proof for this claim has never been published. In this study, we investigated the precise nature of the antigen. Peptide sequences that were obtained from highly purified Sa antigen were unique to vimentin. Recombinant vimentin, however, was not recognized by anti-Sa reference sera. In vivo, vimentin is subjected to various post-translational modifications, including citrullination. Since antibodies to citrullinated proteins are known to be highly specific for RA, we investigated whether Sa is citrullinated and found that Sa indeed is citrullinated vimentin. Anti-Sa antibodies thus belong to the family of anticitrullinated protein/peptide antibodies. The presence of the Sa antigen in RA synovial tissue, and the recent observation that vimentin is citrullinated in dying human macrophages, make citrullinated vimentin an interesting candidate autoantigen in RA and may provide new insights into the potential role of citrullinated synovial antigens and the antibodies directed to them in the pathophysiology of RA.

Keywords:
anticitrullinated protein/peptide antibodies; anti-Sa antibodies; citrullinated vimentin; rheumatoid arthritis; Sa antigen