title: Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies.
abstract: Only a few autoantibodies that are more or less specific for RA have been described so far. The rheumatoid factor most often tested for is not very specific for RA, while the more specific antiperinuclear factor for several reasons is not routinely used as a serological parameter. Here we show that autoantibodies reactive with synthetic peptides containing the unusual amino acid citrulline, a posttranslationally modified arginine residue, are specifically present in the sera of RA patients. Using several citrulline-containing peptide variants in ELISA, antibodies could be detected in 76% of RA sera with a specificity of 96%. Sera showed a remarkable variety in the reactivity pattern towards different citrulline-containing peptides. Affinity-purified antibodies were shown to be positive in the immunofluorescence-based antiperinuclear factor test, and in the so-called antikeratin antibody test, and were reactive towards filaggrin extracted from human epidermis. The specific nature of these antibodies and the presence of these antibodies early in disease, even before other disease manifestations occur, are indicative for a possible role of citrulline-containing epitopes in the pathogenesis of RA.
authors.affiliation: Department of Biochemistry, University of Nijmegen, 6500 HB Nijmegen, The Netherlands. g.schellekens@bioch.kun.nl
authors.forename: G A
authors.initials: GA
authors.lastname: Schellekens
authors.forename: B A
authors.initials: BA
authors.lastname: de Jong
authors.forename: F H
authors.initials: FH
authors.lastname: van den Hoogen
authors.forename: L B
authors.initials: LB
authors.lastname: van de Putte
authors.forename: W J
authors.initials: WJ
authors.lastname: van Venrooij
mesh_terms: D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D002956:Citrulline / Q000276:immunology*; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000276:immunology; D007633:Keratins / Q000276:immunology; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D010455:Peptides; C030902:antiperinuclear factor; D002956:Citrulline; D007633:Keratins