Details

Autor(en) / Beteiligte

• Darrah, Erika
• Andrade, Felipe

Titel

Rheumatoid arthritis and citrullination

Ist Teil von

• Current opinion in rheumatology, 2018-01, Vol.30 (1), p.72-78

Ort / Verlag

United States: Copyright Wolters Kluwer Health, Inc. All rights reserved

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• PURPOSE OF REVIEWDysregulated citrullination is a key element that drives the production and maintenance of antibodies to citrullinated proteins, a hallmark in rheumatoid arthritis (RA). This article reviews recent literature on the origin of citrullinated antigens in RA. RECENT FINDINGSThe study of synovial fluid from patients with RA has provided important insights into the identity of citrullinated proteins that accumulate in the RA joint (the RA citrullinome) and mechanisms that control their generation. SUMMARYCitrullinating enzymes (peptidylarginine deiminases, PADs) are tightly controlled to limit their hyperactivation. Calcium and redox conditions are important regulators of PAD activity. Studies suggest that citrullination is dysregulated both intra- and extracellularly in RA. In neutrophils, host (i.e., perforin and the membrane attack complex) and bacterial (i.e., toxins) pore-forming proteins induce prominent calcium influx, cytolysis, and hyperactivation of PADs. These factors likely drive hypercitrullination in the RA joint and at extraarticular sites of disease initiation, respectively. As oxidizing conditions present in the extracellular environment are known to inactivate PADs, extracellular citrullination in RA probably requires the constant release of active enzymes from dying cells and may be accelerated by autoantibodies that activate PADs.