Fig. 3
From: Clinical and pathophysiologic relevance of autoantibodies in rheumatoid arthritis
Hypothetical role of citrullination in RA. Infiltration of immune cells containing PAD in inflamed tissue (joint). PAD activation due to high intracellular calcium concentration during cell death promotes citrullination of target antigens. Ineffective clearance of apoptotic cell remnants promotes prolonged accessibility of intra-cellular antigens that meet the immune system. Antigen presenting cells (APC) will process and present citrullinated peptides to T cell. In susceptible individuals, activated T cells will activate B cells to generate autoantibodies. This will ultimately result in immune complex formation, followed by upregulation of pro-inflammatory cytokines. Also, ACPA may bind to osteoclasts and thereby promote bone erosion, enhance NET formation by neutrophils and activate complement