Anti-citrullinated protein antibody (ACPA)

Anti-citrullinated protein antibodies (ACPAs) are a diverse group of autoantibodies that specifically recognize proteins containing citrulline, a non-standard amino acid formed by the post-translational deimination of arginine by peptidylarginine deiminase (PAD) enzymes [8, 13]. These antibodies are highly specific for rheumatoid arthritis (RA) and frequently appear in the sera of patients years before the onset of clinical symptoms, serving as a critical diagnostic and prognostic biomarker [9, 11]. Beyond their diagnostic utility, ACPAs are directly pathogenic; they form immune complexes that activate the complement system and trigger the release of pro-inflammatory cytokines such as TNF-α and IL-6 from macrophages [13, 15]. Furthermore, ACPAs can bind to citrullinated proteins on the surface of osteoclasts and neutrophils, directly promoting bone erosion and inducing the release of neutrophil extracellular traps (NETs), which further fuels the autoimmune cycle [8, 15]. Therapeutic strategies traditionally focus on reducing ACPA production via B-cell depletion (e.g., rituximab) or modulating the T-cell help required for their generation (e.g., abatacept) [5, 13]. Emerging therapies are exploring the direct neutralization of ACPAs or the inhibition of PAD enzymes to prevent the formation of the citrullinated neoantigens they target [8, 10].

Other names

Anti-cyclic citrullinated peptide antibodyAnti-CCP antibodyAnti-citrullinated peptide antibodyAnti-mutated citrullinated vimentin antibodyAnti-MCV antibodyAnti-filaggrin antibodyAnti-keratin antibodyAnti-perinuclear factor

B-cell depletion to reduce autoantibody titers, T-cell costimulation blockade to inhibit autoantibody production, and experimental neutralization of citrullinated neoantigens or inhibition of peptidylarginine deiminase (PAD) enzymes.