Rheumatoid arthritis and citrullination
Year: 2017
Type: review
Abstract: PURPOSE OF REVIEW: Dysregulated 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 FINDINGS: The 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. SUMMARY: Citrullinating 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.
Source: Current Opinion in Rheumatology
Authors: Erika Darrah, Felipe Andrade
Institutions: Johns Hopkins University, Johns Hopkins Medicine
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2759236476