Cyclic Citrullinated Peptide Antibody
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Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease that often causes joint swelling, structural destruction, deformity, and dysfunction or loss of function. Because the specific cause of RA is not well understood, the primary goal of treatment is to prevent or delay irreversible joint damage.
Cyclic citrullinated polypeptide antibody is a polypeptide fragment of cyclic poly filament protein, which is an immunoglobulin mainly composed of IgG type, which is an immunoglobulin spontaneously secreted by B lymphocytes of rheumatoid arthritis patients, while B lymphocytes of patients with other diseases and normal people generally do not spontaneously secrete cyclic citrullinated polypeptide antibodies. Therefore, cyclic citrullinated polypeptide antibody is highly specific for rheumatoid arthritis.
In order to improve the antigenicity of the citrullinated peptide chain, Dutch scholar SchellekensGA replaced 2 serines of 19 amino acid residues in the citrullinated peptide chain with cysteine, and then formed disulfide bonds to simulate a cyclic peptide similar to the β-spin structure, called cyclic citrullinated peptide (CCP). Using the CCP can be detected in patients with rheumatoid arthritis (RA) in serum anti CCP antibody, shows its potential in the diagnosis of early rheumatoid arthritis.
What is anti-cyclic citrullinated peptide (Anti-CCP)?
Anti-CCP also called CCP antibody, anti-CCP antibodies, a peptide fragment of a cyclic poly filament protein, mainly an IgG antibody. It has good sensitivity and specificity for rheumatoid arthritis (RA). Patients with RA who were positive for anti-CCP antibodies had more severe bone destruction than those who were negative for anti-CCP antibodies. In studies, anti-CCP antibodies were found to be detectable in patients with early-stage rheumatism, and were present even years before some patients were diagnosed. Anti-CCP antibodies can be used for early diagnosis of rheumatoid arthritis. Rheumatoid arthritis is almost always diagnosed if the patient has a concomitant presence of high rheumatoid factor (excluding other diseases with high rheumatoid factor).
Cyclic citrullinated peptide antibody test
Anti-CCP antibody is an ideal serological marker for early diagnosis of RA. At present, the detection of CCP antibody is mainly performed by enzyme-linked immunosorbent assay (ELISA), latex immunoturbidimetry, and chemiluminescence immunoassay.
Enzyme-linked immunosorbent assay (ELISA)
ELISA is a technology mainly used in the detection of anti-cyclic citrullinated peptide antibodies in the domestic and foreign markets. Through the specific reaction of the antigen and the antibody, the analyte is linked to the enzyme, and then the color reaction between the enzyme and the substrate is used for qualitative or quantitative detection. ELISA has the advantages of high specificity and low cost, but it is usually manual, inefficient, and susceptible to human factors, so automated detection methods have better market prospects.
Immunoturbidimetric Assays
Immunoturbidimetry calculates antigen content by measuring the turbidity of the antigen-antibody binding reaction solution. Latex-enhanced immunoturbidimetry increases the sensitivity of the test by coating an antibody or antigen on a latex particle to increase the volume of antigen-antibody conjugates. The method is simple to operate, has strong anti-interference, and is suitable for the popularization and application of primary medical institutions at all levels.
Chemiluminescence immunoassay
Chemiluminescence immunoassays produce a light signal through a chemical reaction to detect anti-CCP antibodies. This method has high sensitivity and specificity, and is suitable for the detection of a large number of samples.
Significance of anti-CCP antibodies in RA
Rheumatoid arthritis (RA) is one of the common rheumatic immune diseases, and early diagnosis and treatment are essential to control disease progression. Anti-cyclic citrullinated peptide antibody is an important hallmark antibody discovered by scientists in the diagnosis of RA. Anti-CCP antibodies are highly specific and sensitive, able to be detected in the early stages of the disease, and thus play an irreplaceable role in the early diagnosis of RA. In addition, the positive anti-CCP antibody is closely related to the severity of RA, and its presence often predicts exacerbation and poor prognosis, so it is not only an important tool for diagnosing RA, but also an important indicator for evaluating the condition and guiding treatment. The discovery and application of anti-CCP antibodies have greatly improved the diagnostic accuracy and early intervention effect of RA, and provided valuable information for the long-term management of patients.
Fig.1 Possible links between rheumatoid arthritis (RA) specific anti-cyclic citrullinated peptide (anti-CCP) antibodies and RA-associated genetic factors. (Vossenaar Erik R., et al., 2003)
Best indicator for the diagnosis of RA
CCP has a specificity of more than 96.0% for RA. Citrullinated protein is a target antigen involved in the pathogenesis of RA. The corresponding anti-CCP antibody has a higher specificity for the early diagnosis of RA than traditional RF. Although a negative anti-CCP antibody does not completely rule out the possibility of RA disease, a positive anti-CCP antibody indicates a high probability of future development of RA. Because anti-CCP has the characteristics of high sensitivity, strong specificity, and early diagnosis for RA patients, it is of great clinical significance to grasp the effective treatment time window within 2 years.
Correlation with disease changes in RA
The role of anti-CCP antibodies in rheumatoid arthritis is not limited to diagnosis, it is also closely related to the progression and severity of the disease. Anti-CCP antibodies can be secreted by synovial tissue and peripheral blood lymphocytes in patients with RA, so their levels are positively correlated with the degree of bone and joint destruction. Lnane et al. noted that RA patients who were positive for anti-CCP antibodies generally showed higher disease activity, with more severe joint erosion and functional disruption. The study also found a significant correlation between anti-CCP antibody levels and clinical disease activity indicators, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease activity score (DAS28). This suggests that anti-CCP antibodies are not only the hallmark antibodies of RA, but also an important indicator for predicting disease progression and evaluating treatment efficacy.
Summary
In conclusion, citrullination and anti-citrullinated peptide antibodies (ACPA) play a key role in the inflammation of autoimmune diseases such as rheumatoid arthritis. The anti-CCP antibody test is a relatively new test that is able to detect the presence of citrulline antibodies in the blood. Early diagnosis of anti-CCP-positive rheumatoid arthritis is essential for timely targeted therapy, and early detection can help patients maintain quality of life and prevent severe progression of rheumatoid arthritis.
References
- Vossenaar, Erik R., et al., Citrullination, a possible functional link between susceptibility genes and rheumatoid arthritis. Arthritis Res Ther 6 (2003): 1-5.
- Reichert, Stefan, et al., Association of levels of antibodies against citrullinated cyclic peptides and citrullinated α-enolase in chronic and aggressive periodontitis as a risk factor of Rheumatoid arthritis: a case control study. Journal of translational medicine 13 (2015): 1-10.
- Whiting, Penny F., et al., Systematic review: accuracy of anti-citrullinated peptide antibodies for diagnosing rheumatoid arthritis. Annals of internal medicine 152.7 (2010): 456-464.
- Rajalingam, Shamala, et al., Anti-citrullinated cyclic peptide antibody and functional disability are associated with poor sleep quality in rheumatoid arthritis. Archives of Rheumatology 32.1 (2017): 15.
