Hui‑Chun Yua, Ming‑Chi Lua,b*
aDivision of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan, bSchool of Medicine, Tzu Chi University, Hualien, Taiwan
Open Access funded by Buddhist Compassion Relief Tzu Chi Foundation
Abstract
Rheumatoid arthritis (RA) is a common systemic autoimmune disease. Its major manifestation is persistent joint inflammation, which can lead to bone destruction and severe disability. The immunopathogenesis of RA is very complex, involving both innate and adaptive immune systems. Recently, the discovery of anti‑citrullinated protein antibodies (ACPAs) has revolutionized the diagnosis and our understanding of the immunopathogenesis of RA. The presence of ACPAs is also closely linked to the disease activity of RA. Therefore, it is reasonable to believe that ACPAs and protein citrullination are key issues for the development of RA. We have summarized the recent study results in this review. The first theory concerning the pathogenesis of RA proposed that ACPAs
link the well‑known genetic and environmental risk factors for developing RA. However, due to the close association between joint inflammation and ACPAs, a more direct role of ACPAs in the immunopathogenesis of RA is anticipated. Within the past 10 years, many
studies, including some of our own, have shown that ACPAs can promote an inflammatory response through complement activation, formation of neutrophil extracellular traps, and direct binding to key players, including monocytes, osteoclasts, and osteoblasts, in the
mediation of bone destruction in the joints of RA patients. We also present some new perspectives and issues that need to be further investigated.
Keywords: Anti‑citrullinated protein antibodies, Citrullination, Peptidylarginine deiminase, Rheumatoid arthritis
