Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects millions of people worldwide. Early and accurate diagnosis is essential for effective treatment and management of the condition. One of the most reliable diagnostic tools for RA is the Cyclic Citrullinated Peptide IgG test. This test detects anti-CCP antibodies, which are strongly associated with RA.
In this article, we explore the science behind CCP antibodies, the role of citrullination in autoimmunity, the CCP IgG test procedure, result interpretation, and its diagnostic significance in rheumatoid arthritis.
What Are Cyclic Citrullinated Peptides (CCP)?
Cyclic citrullinated peptides (CCPs) are artificially synthesized proteins that mimic citrullinated proteins found in the body. Citrullination is a natural post-translational modification where the amino acid arginine is converted into citrulline by an enzyme called peptidylarginine deiminase (PAD).
In healthy individuals, citrullination occurs in response to inflammation and does not trigger an immune reaction. However, in rheumatoid arthritis, the immune system mistakenly recognizes citrullinated proteins as foreign and produces autoantibodies against them, known as anti-CCP antibodies.
The Role of CCP Antibodies in Rheumatoid Arthritis
Anti-CCP antibodies are considered highly specific markers for RA. Their presence in the blood suggests an autoimmune response targeting citrullinated proteins in the joints, leading to:
- Chronic inflammation
- Joint pain, stiffness, and swelling
- Erosive joint damage
Sensitivity and Specificity of Anti-CCP in RA
- Sensitivity: 70-80% (Indicates how often the test correctly identifies RA patients.)
- Specificity: 95-100% (Indicates how often the test correctly identifies people without RA.)
Compared to rheumatoid factor (RF), the CCP IgG test is more specific. While RF can be present in other autoimmune diseases, anti-CCP antibodies are strongly linked to RA.
The Role of CCP Antibodies in Rheumatoid Arthritis
Anti-CCP antibodies are considered highly specific markers for RA. Their presence in the blood suggests an autoimmune response targeting citrullinated proteins in the joints, leading to:
- Chronic inflammation
- Joint pain, stiffness, and swelling
- Erosive joint damage
Sensitivity and Specificity of Anti-CCP in RA
- Sensitivity: 70-80% (Indicates how often the test correctly identifies RA patients.)
- Specificity: 95-100% (Indicates how often the test correctly identifies people without RA.)
Compared to rheumatoid factor (RF), the CCP IgG test is more specific. While RF can be present in other autoimmune diseases, anti-CCP antibodies are strongly linked to RA.
How Is the CCP IgG Test Performed?
The CCP IgG test is a blood test that detects anti-CCP antibodies in the bloodstream.
Procedure
- A blood sample is drawn from a vein in the arm or a finger prick.
- The sample is sent to a laboratory for analysis.
- The test results are reported in units per milliliter (U/mL).
Interpreting Test Results
| CCP IgG Levels (U/mL) | Interpretation |
|---|---|
| <20 U/mL | Negative (Low likelihood of RA) |
| 20-39 U/mL | Weak positive (Possible early-stage RA) |
| ≥40 U/mL | Strong positive (High likelihood of RA) |
- A positive result suggests RA, but further clinical evaluation is needed.
- A negative result does not rule out RA, as seronegative RA can occur.
Why Is the CCP IgG Test Important for RA Diagnosis?
1. Early Detection and Treatment
Anti-CCP antibodies can appear in the blood years before RA symptoms develop. This makes the test valuable for early intervention, which can slow disease progression and prevent joint damage.
2. Distinguishing RA from Other Conditions
The high specificity of the CCP test helps differentiate RA from other autoimmune diseases like lupus (SLE), psoriatic arthritis, and juvenile idiopathic arthritis.
3. Predicting RA Severity
Patients with high CCP antibody levels often experience more severe joint damage and inflammation over time.
Limitations of the CCP IgG Test
While highly useful, the CCP IgG test is not 100% conclusive on its own. Limitations include:
- False negatives – Some RA patients test negative, especially in early disease stages.
- False positives – Up to 10-15% of lupus (SLE) patients and a small percentage of healthy individuals may test positive.
- Not a standalone test – Requires additional tests like rheumatoid factor (RF), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and imaging (X-rays, MRI) for confirmation.
Additional Testing and Disease Monitoring
To confirm an RA diagnosis, doctors may order additional tests, including:
1. Rheumatoid Factor (RF) Test
- Detects RF antibodies, which are found in 70-80% of RA patients.
- Less specific than CCP, as RF can be present in lupus, Sjögren’s syndrome, and chronic infections.
2. Inflammatory Markers (CRP & ESR Tests)
- C-reactive protein (CRP): Measures inflammation levels in the body.
- Erythrocyte sedimentation rate (ESR): High levels suggest ongoing inflammation.
3. Imaging Tests
- X-rays, MRI, and ultrasound help assess joint damage and disease progression.
4. Follow-Up CCP Testing
- Repeated CCP IgG testing may help track disease progression and treatment response.
Risks and Considerations for CCP IgG Testing
The CCP IgG test is a low-risk blood test. However, minor side effects at the blood draw site may include:
- Mild pain
- Bruising
- Lightheadedness (rare)
Since CCP antibody levels alone do not confirm RA, consulting a rheumatologist is essential for accurate diagnosis and treatment planning.
Preparing for a CCP IgG Test
- Inform your doctor about any medications or supplements you are taking.
- No fasting required before the test.
- Wear loose-fitting clothing for easy blood draw access.
FAQs About Cyclic Citrullinated Peptide IgG
The cyclic citrullinated peptide antibody IgG test is used to diagnose rheumatoid arthritis (RA) and is part of the anti-cyclic citrullinated peptide (anti-CCP) antibodies blood test. It helps identify the presence of specific antibodies that target citrullinated peptides, which are associated with RA and connective tissue diseases.
CCP antibodies can be detected in up to 10%–15% of patients with systemic lupus erythematosus (SLE). Therefore, it is possible that some individuals with lupus will test positive for CCP.
Additional tests, such as X-rays, MRI, ultrasound, ESR and CRP tests may be needed alongside the CCP IgG test to confirm a diagnosis of rheumatoid arthritis.
A CCP IgG test is a simple blood test. A small amount of blood is drawn from a vein in the arm and sent to a laboratory for analysis.
Conclusion
The CCP IgG test is a highly specific and valuable tool for diagnosing rheumatoid arthritis. While a positive result strongly indicates RA, additional tests and clinical evaluation are required for a definitive diagnosis.
Early detection through CCP IgG testing allows for timely treatment, helping to slow disease progression and preserve joint function. If you experience joint pain, swelling, or stiffness, consult your doctor about CCP IgG testing as part of a comprehensive RA diagnosis and management plan.
Scientific Research References:
1. Verpoort, K. N., Jol‐Van Der Zijde, C. M., Papendrecht‐Van Der Voort, E. A. M., Ioan‐Facsinay, A., Drijfhout, J. W., Van Tol, M. J. D., … & Toes, R. E. M. (2006). Isotype distribution of anti–cyclic citrullinated peptide antibodies in undifferentiated arthritis and rheumatoid arthritis reflects an ongoing immune response. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology, 54(12), 3799-3808.
2. György, B., Tóth, E., Tarcsa, E., Falus, A., & Buzás, E. I. (2006). Citrullination: a posttranslational modification in health and disease. The international journal of biochemistry & cell biology, 38(10), 1662-1677.
3. Wang, W., & Li, J. (2011). Identification of natural bispecific antibodies against cyclic citrullinated peptide and immunoglobulin G in rheumatoid arthritis. PLoS One, 6(1), e16527.
4. Van Gaalen, F. A., Linn‐Rasker, S. P., Van Venrooij, W. J., De Jong, B. A., Breedveld, F. C., Verweij, C. L., … & Huizinga, T. W. J. (2004). Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study. Arthritis & Rheumatism, 50(3), 709-715.
5. Pramod, G. R., Dihingia, P., Jha, A. K., Gadgade, A., & Agarwal, D. (2022). Rheumatoid arthritis co-relation with anti-CCP antibodies with special reference to its prevalence in asymptomatic first-degree relatives. Mediterranean Journal of Rheumatology, 33(1), 42.
6. E Witalison, E., R Thompson, P., & J Hofseth, L. (2015). Protein arginine deiminases and associated citrullination: physiological functions and diseases associated with dysregulation. Current drug targets, 16(7), 700-710.
7. Raptopoulou, A., Sidiropoulos, P., Katsouraki, M., & Boumpas, D. T. (2007). Anti-citrulline antibodies in the diagnosis and prognosis of rheumatoid arthritis: evolving concepts. Critical reviews in clinical laboratory sciences, 44(4), 339-363.
8. Mikuls, T. R., O’Dell, J. R., Stoner, J. A., Parrish, L. A., Arend, W. P., Norris, J. M., & Holers, V. M. (2004). Association of rheumatoid arthritis treatment response and disease duration with declines in serum levels of IgM rheumatoid factor and anti–cyclic citrullinated peptide antibody. Arthritis & Rheumatism, 50(12), 3776-3782.
9. Nishimura, K., Sugiyama, D., Kogata, Y., Tsuji, G., Nakazawa, T., Kawano, S., … & Kumagai, S. (2007). Meta-analysis: diagnostic accuracy of anti–cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Annals of internal medicine, 146(11), 797-808.
10. Xiao, X. Y. (2017). The changes and clinical significance of anti CCP antibodies, complement and immunoglobulin in the pathological process of rheumatoid arthritis. Journal of Hainan Medical University, 23(4), 94-97.
11. Kakumanu, P., Sobel, E. S., Narain, S., Li, Y., Akaogi, J., Yamasaki, Y., … & Satoh, M. (2009). Citrulline dependence of anti-cyclic citrullinated peptide antibodies in systemic lupus erythematosus as a marker of deforming/erosive arthritis. The Journal of rheumatology, 36(12), 2682-2690.
12. Sokolove, J., Johnson, D. S., Lahey, L. J., Wagner, C. A., Cheng, D., Thiele, G. M., … & Robinson, W. H. (2014). Rheumatoid factor as a potentiator of anti–citrullinated protein antibody–mediated inflammation in rheumatoid arthritis. Arthritis & rheumatology, 66(4), 813-821
13. Grassi, W., De Angelis, R., Lamanna, G., & Cervini, C. (1998). The clinical features of rheumatoid arthritis. European journal of radiology, 27, S18-S24.
14. Arslan, A., Farooq, S. M. Y., Sugrah, S. K. T., Gilani, S. A., Iqbal, A., Gilani, H. S. A., … & Manzoor, M. (2022). Ultrasonographic assessment of rheumatoid arthritis: A systematic review. The Professional Medical Journal, 29(08), 1181-1190.
15. Wendel, S., Fontão‐Wendel, R., Fachini, R., Candelaria, G., Scuracchio, P., Achkar, R., … & Durigon, E. (2021). A longitudinal study of convalescent plasma (CCP) donors and correlation of ABO group, initial neutralizing antibodies (nAb), and body mass index (BMI) with nAb and anti‐nucleocapsid (NP) SARS‐CoV‐2 antibody kinetics: Proposals for better quality of CCP collections. Transfusion, 61(5), 1447-1460.
