ACPAs Are Much More Than Diagnostic Autoantibodies

Area of Science:

• Immunology
• Rheumatology

Background:

• Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and damage.
• Anti-citrullinated protein autoantibodies (ACPAs) are highly specific biomarkers for RA and are implicated in its pathogenesis.

Approach:

• This review synthesizes current research on the pathogenic mechanisms of ACPAs in RA.
• Focuses on in vitro evidence demonstrating ACPA-induced cellular and molecular responses relevant to RA.

Key Points:

• ACPAs target various citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen.
• In vitro studies show ACPAs stimulate macrophage TNF-α production, osteoclastogenesis, complement activation, and NET formation.
• ACPAs contribute to pathogenic cytokine expression and oxidative stress in immune cells from RA patients.

Conclusions:

• ACPAs play a significant pathogenic role in rheumatoid arthritis, contributing to joint destruction and extra-articular manifestations.
• Understanding ACPA-mediated mechanisms is crucial for developing targeted RA therapies.