CITRULLINE IS AN ESSENTIAL CONSTITUENT OF ANTIGENIC DETERMINANTS RECOGNIZED BY RHEUMATOID ARTHRITIS-SPECIFIC AUTOANTIBODIES

Only a few autoantibodies that are more or less specific for RA have b een described so far. The rheumatoid factor most often tested for is n ot very specific for RA, while the more specific antiperinuclear facto r for several reasons is not routinely used as a serological parameter , Here we show that autoantibodies reactive with synthetic peptides co ntaining the unusual amino acid citrulline, a posttranslationally modi fied arginine residue, are specifically present in the sera of RA pati ents, Using several citrulline-containing peptide variants in ELISA, a ntibodies 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 antiperinuc lear factor test, and in the so-called antikeratin antibody test, and were reactive towards filaggrin extracted from human epidermis. The sp ecific 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 t he pathogenesis of RA.