Anti-CCP antibodies are potentially important surrogate markers for diagnosis and prognosis in rheumatoid arthritis (RA), because they are as sensitive as, and more specific than, IgM rheumatoid factors (RF) in early and fully established disease

may predict the eventual development into RA when found in undifferentiated arthritis

are a marker of erosive disease in RA may be detected in healthy individuals years before onset of clinical RA. Citrulline is a non-standard amino acid, created by de-imination of arginine residues in several proteins by the action of peptidylarginine deiminase (PAD). There are several isotypes of this enzyme; in the inflammatory RA synovium, PAD 2 and PAD 4 are abundant. These enzymes cause the local citrullination of synovial proteins, such as fibrin. Interestingly, citrullinated peptides fit better in the HLA DR4 (DRB1*0401 or *0404) antigen binding grooves than the corresponding arginine containing peptides, findings that link this immune response to the shared epitope hypothesis of RA pathophysiology.  The citrulline moiety is the true determinant on proteins recognized by APF, AKA, and possibly anti-Sa.

There are several versions of test for ACPAs with different sensitive and specificities. I have attached two references that give additional information regarding the performance of these tests.

Best regards,

David Anderson

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Anti-CCP positivity overall is highly specific for RA, about 97%-98%, as above-mentioned with a sensitivity comparable to the old RA factor test. However, it has also been described in other entities such as psoriatic arthritis (PsA), other autoimmune disorders, mycobacterial infections, etc.