Purpose and Interpretation of Cyclic Citrullinated Peptide (CCP) Antibody Test in Rheumatoid Arthritis
The anti-CCP antibody test is a highly specific diagnostic tool for rheumatoid arthritis (RA) that helps identify patients early in the disease course and predicts those likely to develop severe, erosive disease requiring aggressive treatment. 1, 2
Diagnostic Value
- Anti-CCP antibody testing has superior specificity (approximately 95%) compared to rheumatoid factor (RF) testing (less than 90%) for diagnosing RA, though with comparable sensitivity (>70%) 3
- The test should be performed in patients with suspected persistent synovitis, particularly when small joints of hands/feet are affected, multiple joints are involved, or symptoms have persisted for ≥3 months 4, 5
- Anti-CCP antibodies can be detected very early in the disease process, often before clinical manifestations become apparent, making it valuable for early diagnosis 3
- Consider measuring anti-CCP antibodies in people with suspected RA who are negative for rheumatoid factor, especially when combination therapy is being considered 4, 1
- When used together with RF testing, the specificity for diagnosing RA increases to nearly 99.6%, significantly improving diagnostic accuracy 6
Prognostic Value
- Anti-CCP positivity is a strong predictor of progression from undifferentiated arthritis to definitive RA 4, 1
- The presence of anti-CCP antibodies is associated with more aggressive disease and increased risk of developing erosive joint damage 1, 2
- In patients with musculoskeletal symptoms without clinical arthritis, high anti-CCP levels strongly correlate with progression to clinical arthritis development 1
- Dual positivity for both anti-CCP and RF indicates higher risk of arthritis development in patients with seropositive arthralgia 1
- The European League Against Rheumatism recommends measuring anti-CCP antibodies as one of the key factors for predicting persistent and erosive disease 1
Clinical Application
- Anti-CCP antibodies are included in the 2010 American College of Rheumatology/EULAR classification criteria for RA, contributing significantly to the diagnostic score 1
- For patients at risk of developing persistent or erosive arthritis based on anti-CCP positivity, early initiation of disease-modifying antirheumatic drugs (DMARDs) is recommended, even before fulfilling established classification criteria 1
- A diagnostic approach combining anti-CCP2 assay with RF, CRP, and assessment of swollen joints (>3) provides extremely high specificity (98.7%) and positive predictive value (95.5%) for RA diagnosis within 24 months of symptom onset 7
- Anti-CCP testing is particularly valuable in seronegative (RF-negative) patients with suspected RA, as it may be the only positive serological marker 4, 5
Limitations and Considerations
- Despite high specificity, anti-CCP antibody testing has moderate sensitivity (41-78.9% in various studies), meaning a negative result does not exclude RA 2, 6, 8
- Anti-CCP antibodies can occasionally be detected in patients with bronchiectasis, particularly those who may later develop RA 1
- In cancer patients receiving checkpoint inhibitors, pre-existing ACPAs may identify those at risk of developing RA as an immune-related adverse event 1
- Point-of-care rapid tests for anti-CCP have shown comparable sensitivity and specificity to laboratory ELISA methods, potentially enabling earlier diagnosis in primary care settings 8
Interpretation of Results
- At a cutoff value of 50 units, anti-CCP testing typically shows sensitivity of approximately 41% and specificity of 97.8% 6
- Anti-CCP-positive RA patients typically have high antibody concentrations (mean 1100 units, range 57-3419 units), while negative patients and controls show much lower values (mean 6.8-7.6 units, range 1-39 units) 6
- The extent of the ACPA (anti-citrullinated protein antibody) repertoire correlates with disease severity and progression risk 1