Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies.

TLDR

Only a few rheumatoid‑arthritis–specific autoantibodies have been described, and the commonly tested rheumatoid factor lacks specificity while the more specific antiperinuclear factor is not routinely used. The study employed ELISA with multiple citrulline‑containing peptide variants to detect anti‑citrulline antibodies in patient sera. Anti‑citrulline antibodies were identified in 76 % of RA sera with 96 % specificity, displayed diverse reactivity patterns across peptides, were positive in antiperinuclear and antikeratin tests, reacted with filaggrin, and appeared early in disease before other manifestations, suggesting a pathogenic role for citrullinated epitopes.

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.