Antibodies against cyclic citrullinated peptides (Anti-CCP antibodies; anti-citrullinated peptide antibodies, ACPA)

Abstract

Anti-CCP antibodies (ACPA) have a high specificity and sensitivity for rheumatoid arthritis (RA). They belong to the IgG class and have more than 56% sensitivity and more than 90% specificity for RA, depending on the assay kit used. They are directed against peptides and proteins, which possess the unusual, non-standard amino acid citrulline. Citrullinated proteins develop during enzymatic post-translation enzymatic deimination of arginine residues catalysed by peptidylarginine deiminases in the presence of Ca²⁺. Such post-translational modification of proteins leads to loss of the positive charge of arginine residues with subsequent modification of antigenicity of the proteins. Antiperinuclear factor, antikeratin antibodies (both directed against citrullinated filaggrin), anti-Sa antibodies (against citrullinated vimentin) and cyclic citrullinated peptide antibodies (anti-CCP) are among the best-known citrullinated reactive antibodies associated with RA.