Rheumatoid arthritis and citrullination

Area of Science:

• Rheumatology
• Immunology
• Biochemistry

Background:

• Rheumatoid arthritis (RA) is characterized by antibodies to citrullinated proteins.
• Citrullination, the modification of arginine residues to citrulline, is central to RA pathogenesis.

Purpose of the Study:

• To review recent literature on the origins of citrullinated antigens in rheumatoid arthritis.
• To explore the mechanisms driving dysregulated citrullination in RA.

Main Methods:

• Review of current scientific literature on citrullination in RA.
• Analysis of findings from studies on synovial fluid in RA patients.

Main Results:

• The RA citrullinome, comprising citrullinated proteins in the RA joint, has been identified.
• Mechanisms controlling the generation of citrullinated proteins in RA have been elucidated.
• Dysregulated citrullination occurs both intracellularly and extracellularly in RA.

Conclusions:

• Peptidylarginine deiminases (PADs) are tightly regulated, with calcium and redox conditions influencing their activity.
• Neutrophil activation by pore-forming proteins leads to calcium influx, cytolysis, and PAD hyperactivation, driving hypercitrullination.
• Extracellular citrullination in RA may involve the release of active PADs from dying cells and acceleration by autoantibodies.