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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 4/2008

Open Access 01-08-2008 | Research article

Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis

Authors: Xiaoyan Zhao, Nwora Lance Okeke, Orr Sharpe, Franak M Batliwalla, Annette T Lee, Peggy P Ho, Beren H Tomooka, Peter K Gregersen, William H Robinson

Published in: Arthritis Research & Therapy | Issue 4/2008

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Abstract

Introduction

There is increasing evidence that autoantibodies and immune complexes (ICs) contribute to synovitis in rheumatoid arthritis (RA), yet the autoantigens incorporated in ICs in RA remain incompletely characterised.

Methods

We used the C1q protein to capture ICs from plasma derived from human RA and control patients. Antibodies specific for immunoglobulin were used to detect ICs, and fibrinogen antibodies were used to detect fibrinogen-containing ICs. RA and control plasma were separated by liquid chromatography, and fractions then characterised by ELISA, immunoblotting and mass spectrometry. Immunohistochemical staining was performed on rheumatoid synovial tissue.

Results

C1q-immunoassays demonstrated increased levels of IgG (p = 0.01) and IgM (p = 0.0002) ICs in plasma derived from RA patients possessing anti-cyclic citrullinated peptide (CCP+) autoantibodies as compared with healthy controls. About one-half of the anti-CCP+ RA possessed circulating ICs containing fibrinogen (p = 0.0004). Fractionation of whole RA plasma revealed citrullinated fibrinogen in the high molecular weight fractions that contained ICs. Positive correlations were observed between fibrinogen-containing ICs and anti-citrullinated fibrinogen autoantibodies, anti-CCP antibody, rheumatoid factor and certain clinical characteristics. Immunohistochemical staining demonstrated co-localisation of fibrinogen, immunoglobulin and complement component C3 in RA pannus tissue. Mass spectrometry analysis of immune complexes immunoprecipitated from RA pannus tissue lysates demonstrated the presence of citrullinated fibrinogen.

Conclusion

Circulating ICs containing citrullinated fibrinogen are present in one-half of anti-CCP+ RA patients, and these ICs co-localise with C3 in the rheumatoid synovium suggesting that they contribute to synovitis in a subset of RA patients.
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Metadata
Title
Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis
Authors
Xiaoyan Zhao
Nwora Lance Okeke
Orr Sharpe
Franak M Batliwalla
Annette T Lee
Peggy P Ho
Beren H Tomooka
Peter K Gregersen
William H Robinson
Publication date
01-08-2008
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 4/2008
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2478

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