Inhibiting citrullination in rheumatoid arthritis: taking fuel from the fire

• Published in: Arthritis research & therapy Vol. 14; no. 1; p. 108
• Main Authors: Fisher, Benjamin Ac, Venables, Patrick J
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 01.01.2012; BioMed Central
• Subjects: Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Citrulline - metabolism; Female; Glucocorticoids - therapeutic use; Humans; Male; Synovial Membrane - drug effects
• ISSN: 1478-6354; 1478-6362
• DOI: 10.1186/ar3740

Citrullination is a post-translational modification catalysed by peptidylarginine deiminase and is a common feature of inflammation. The presence of anti-citrullinated protein/peptide antibodies (ACPA), however, is unique to rheumatoid arthritis. Several lines of evidence suggest that ACPA are important in the pathogenesis of rheumatoid arthritis. A popular hypothesis for this pathogenesis is a two-hit model. The first hit gives rise to ACPA, and the second hit, an unrelated episode of synovial inflammation accompanied by citrullination, is perpetuated by the pre-existing antibodies. This model suggests that reducing citrullination might ameliorate disease. Recent findings indicate that citrullination closely correlates with inflammation, and that glucocorticoids decrease peptidylarginine deiminase expression independent of their other anti-inflammatory effects.