Rethink about the role of rheumatoid factor and anti-citrullinated protein antibody in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by joint inflammation and extra-articular manifestations. Many questions in the pathogenesis, clinical manifestation, and disease spectrum are answered after the discovery of the first autoantibody namely rheumatoid factor (RF). The finding of the second autoantibody named anti-citrullinated protein antibody (ACPA), which unearths the importance of protein citrullination process. It further provides the insight how immune cells and complement interact to perpetuate the inflammatory response. These two autoantibodies pave the way for our better understanding of RA. This review article focuses on the history, pathophysiology, and clinical association of these two autoantibodies in RA.