Anticitrulina

Anticitrulina, more commonly referred to as anti-citrullinated protein antibodies (ACPA), are autoantibodies directed against citrullinated peptides and proteins. Citrullination is a post-translational modification in which arginine residues are converted to citrulline by peptidylarginine deiminase (PAD) enzymes, a process enhanced in inflamed tissues such as the synovium.

In clinical practice, ACPA are highly specific for rheumatoid arthritis (RA). They can precede the onset of arthritis by months or years and are found in about 60–80% of RA patients, with specificity around 95% when tested for anti-cyclic citrullinated peptide antibodies. The presence of ACPA is associated with more aggressive disease and greater likelihood of radiographic joint damage. ACPA status is incorporated into RA classification criteria (ACR/EULAR 2010).

Detection and interpretation: The most common assays detect anti-CCP antibodies (e.g., CCP‑2). Testing may be combined with rheumatoid factor (RF) to improve sensitivity, though RF reduces specificity. ACPA testing is generally recommended when inflammatory arthritis is suspected or when RA is being differentiated from other conditions.

Pathogenesis: The production of anticitrullinated antibodies requires genetic predisposition, notably HLA-DRB1 alleles encoding the shared epitope, and environmental triggers such as smoking. The immune response targets citrullinated proteins including vimentin, fibrinogen, and α-enolase, among others. Epitope spreading can occur, expanding the antibody repertoire during disease.

Limitations and scope: Not all RA patients are ACPA-positive; approximately 20–40% may be seronegative. ACPA may rarely be found in other autoimmune diseases or healthy individuals at low levels. Positive ACPA supports RA diagnosis but is not definitive in isolation; clinical context and imaging remain essential.

Terminology: In some languages the term anticitrulina is used to refer to these antibodies; in English, ACPA or anti-CCP antibodies are standard terms.