Ann Rheum Dis

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The most recent version of this article was published on 1 August 2006

Ann Rheum Dis. Published Online First: 31 January 2006. doi:10.1136/ard.2005.044743
Copyright © 2006 BMJ Publishing Group Ltd & European League Against Rheumatism
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Extended Report

Citrullinated fibrinogen detected as a soluble citrullinated autoantigen in rheumatoid arthritis synovial fluids

Yasunobu Takizawa 1, Akari Suzuki 2, Tetsuji Sawada 3*, Mizuko Ohsaka 2, Tetsufumi Inoue 4, Ryo Yamada 2 and Kazuhiko Yamamoto 3

1 The University of Tokyo, Japan
2 The Institute of Physical and Chemical Research (RIKEN), Japan
3 University of Tokyo, Japan
4 Tokyo University of Foreign Studies, Japan

* To whom correspondence should be addressed. E-mail: tetsuji-tky{at}umin.ac.jp.

Accepted 24 January 2006


*  Abstract

Background: Anti-citrullinated protein antibodies (ACPA) are specifically and frequently detected in rheumatoid arthritis (RA) patients' sera. Citrullinated fibrin or fibrinogen is a candidate autoantigen of such antibodies.

Objective: To investigate the presence of citrullinated fibrinogen (cFBG) in the plasma or synovial fluid of RA and control patients and to determine cFBG levels and their relationship with serum markers for RA if it is present.

Methods: A sandwich enzyme-linked immunosorbent assay (ELISA) to measure cFBG was established using monoclonal antibodies (mAbs) cF16.1 and cF252.1, generated by immunizing mice with R16Cit and R252Cit, the fibrinogen A{alpha} chain -derived sequences with citrulline at position 16 and 252 respectively, and the presence of cFBG was further investigated with immunoprecipitation- Western blot.

Results: Positive signals were detected in 11 of 15 RA synovial fluids (RASFs), but not in OA synovial fluids or RA plasma with sandwich ELISA for cFBG using cF16.1 and an anti-modified citrulline antibody (AMC). The presence of cFBG in RASFs was confirmed with immunoprecipitation- Western blot. Furthermore, most RA sera strongly reacted against R16Cit. No relationship was observed between RASF cFBG levels and C-reactive protein or anti cyclic citrullinated peptide antibody levels of the paired sera.

Conclusion: cFBG is detected as a soluble citrullinated autoantigen in RASFs and may therefore be a genuine candidate antigen for ACPA in RA patients.

Keywords: anti citrulline-containing peptide antibody, citrullinated fibrinogen, position16 of fibrinogen Aalpha chain, rheumatoid arthritis, synovial fluid






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