The rheumatoid arthritis (RA) cycle. Model for the role of protein citrullination in the pathophysiology of RA. The various aspects of the five major steps are depicted. Step 1, entry and death of inflammatory cells in the synovium; step 2, peptidylarginine deiminase (PAD) activation and protein citrullination; step 3, immune response to citrullinated antigens; step 4, formation of citrullinated immune complexes and their effects; step 5, recruitment of new inflammatory cells. ACPA, anti-citrullinated protein/peptide antibody.