title: Elevated levels of fibrinogen-derived endogenous citrullinated peptides in synovial fluid of rheumatoid arthritis patients.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the joints and the presence of autoantibodies directed against proteins containing the non-standard arginine-derived amino acid citrulline. The protein fibrinogen, which has an essential role in blood clotting, is one of the most prominent citrullinated autoantigens in RA, particularly because it can be found in the inflamed tissue of affected joints. Here, we set out to analyze the presence of citrullinated endogenous peptides in the synovial fluid of RA and arthritic control patients.
  
  
  METHODS
  Endogenous peptides were isolated from the synovial fluid of RA patients and controls by filtration and solid phase extraction. The peptides were identified and quantified using high-resolution liquid chromatography-mass spectrometry.
  
  
  RESULTS
  Our data reveal that the synovial fluid of RA patients contains soluble endogenous peptides, derived from fibrinogen, containing significant amounts of citrulline residues and, in some cases, also phosphorylated serine. Several citrullinated peptides are found to be more abundantly present in the synovial fluid of RA patients compared to patients suffering from other inflammatory diseases affecting the joints.
  
  
  CONCLUSIONS
  The increased presence of citrullinated peptides in RA patients points toward a possible specific role of these peptides in the immune response at the basis of the recognition of citrullinated peptides and proteins by RA patient autoantibodies.
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University and Netherlands Proteomics Centre, Padualaan 8, Utrecht, 3584 CH, The Netherlands. r.raijmakers@uu.nl
authors.forename: Reinout
authors.initials: R
authors.lastname: Raijmakers
authors.forename: Joyce J B C
authors.initials: JJ
authors.lastname: van Beers
authors.forename: Mahmoud
authors.initials: M
authors.lastname: El-Azzouny
authors.forename: Natasja F C
authors.initials: NF
authors.lastname: Visser
authors.forename: Borut
authors.initials: B
authors.lastname: Božič
authors.forename: Ger J M
authors.initials: GJ
authors.lastname: Pruijn
authors.forename: Albert J R
authors.initials: AJ
authors.lastname: Heck
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D001324:Autoantigens / Q000032:analysis*; D002853:Chromatography, Liquid; D002956:Citrulline / Q000276:immunology / Q000378:metabolism; D005340:Fibrinogen / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D010455:Peptides / Q000032:analysis*; D013582:Synovial Fluid / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001324:Autoantigens; D010455:Peptides; D002956:Citrulline; D005340:Fibrinogen