What are anti citrullinated protein antibodies (ACPAs) and how are they tested for?
ACPAs are directed against citrulline residues on various proteins formed by post-translational deimination of arginine by the enzyme peptidylarginine deiminase. Commercial assays have been developed to identify some of these antibodies. The tests utilize a cyclic peptide substrate engineered to mimic the shape of proteins in antibody-peptide complexes. The resulting cyclic citrullinated peptide (CCP) results in higher affinity antibody binding than linear peptide substrates, thereby improving the sensitivity of the assay. These antibodies are found in patients with RA with a sensitivity similar to RF (75%), but with increased specificity (90%–95%). Notably some RA patients (10%) may be negative for RF but positive for anti-CCP.
There is good evidence for an association of anti-CCP with more rapid radiological joint damage in RA patients. The high specificity of anti-CCP antibodies helps to diagnostically separate RA from other diseases, such as hepatitis C, which can present with polyarthralgias and a positive RF that resembles RA but have negative anti-CCP antibodies.