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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.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>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.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>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.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar2478","type":"journal-article","created":{"date-parts":[[2008,8,19]],"date-time":"2008-08-19T06:14:50Z","timestamp":1219126490000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":156,"title":["Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis"],"prefix":"10.1186","volume":"10","author":[{"given":"Xiaoyan","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nwora Lance","family":"Okeke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orr","family":"Sharpe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franak M","family":"Batliwalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette T","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy P","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beren H","family":"Tomooka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter K","family":"Gregersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2008,8,18]]},"reference":[{"key":"2327_CR1","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/nature01661","volume":"423","author":"GS Firestein","year":"2003","unstructured":"Firestein GS: Evolving concepts of rheumatoid arthritis. 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