ACPAs Are Much More Than Diagnostic Autoantibodies.
Anti-citrullinated protein autoantibodies (ACPAs) are the major autoantibodies in rheumatoid arthritis (RA). Anti-citrullinated protein autoantibodies are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. Presence of ACPA is associated with joint damage and extra-articular manifestations, suggesting that ACPAs are most likely pathogenic autoantibodies in RA. In vitro, ACPAs induce macrophage tumor necrosis factor alpha (TNF-α) production, osteoclastogenesis, and complement activation. These autoantibodies also induce the formation of neutrophil extracellular traps (NETs). Additionally, ACPAs induce pathogenic cytokines expression and oxidative stress in immune cells derived from RA patients. The aim of this review is to show the pathogenic roles of these autoantibodies in RA.
Department of Medicine "B", Sheba Medical Center, Tel-Hashomer, Israel; Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer Israel; and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Abdulla
A
Watad
Department of Medicine "B", Sheba Medical Center, Tel-Hashomer, Israel; Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer Israel; and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Howard
H
Amital