Cyclic Citrullinated Peptide Antibody

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In order to improve the antigenic activity of citrullinated peptide chain and overcome the deficiency of linear citrulline peptide chain, Dutch scholar SchellekensGA replaced two serine from the 19 amino acid residues in a citrulline peptide chain with cysteine, and cyclized cysteine to form a disulfide bond similar to the β-rotation structure to form cyclic citrullinated peptide (CCP). Its amino acid sequence is listed as HQCHQESTXGRSRGRCGRSGS (“S” represents disulfide bond, “X” means citrulline, other letters are common amino acid single letter marks), and successfully detected anti-CCP antibody in the serum of patients with rheumatoid arthritis, and found that it can be used for early diagnosis of rheumatoid arthritis, which has attracted great attention of scholars.

Introduction of Anti-CCP Antibody

Anti-CCP antibody is a peptide fragment of cyclic polyfilament protein, which is mainly IgG antibody. It has good sensitivity and specificity to rheumatoid arthritis (RA). The bone destruction in RA patients with positive anti-CCP antibody is more serious than that in patients with negative anti-CCP antibody. In the study, it is found that anti-CCP antibodies can be detected in patients with early rheumatism, and even anti-CCP antibodies exist in some patients a few years before they are diagnosed. Anti-CCP antibody can be used for the early diagnosis of rheumatoid arthritis. If patients have high rheumatoid factor at the same time (excluding other diseases with high rheumatoid factor), rheumatoid arthritis can be diagnosed basically.

Diagnostic significance of Anti-CCP Antibody in Rheumatoid Arthritis

Rheumatic immune disease is a group of diseases with disorders of the autoimmune system, and there are often a series of positive autoantibodies, which are of great significance for diagnosis, evaluation of prognosis and guidance of treatment. Therefore, it is necessary to find appropriate autoantibodies. Anti-CCP antibody is a marker antibody that scientists are actively looking for for the diagnosis of rheumatoid arthritis.

Figure 1 Possible links between rheumatoid arthritis (RA) specific anti-cyclic citrullinated peptide (anti-CCP) antibodies and RA-associated genetic factors.

• CCP can be used as the best index for auxiliary diagnosis of RA.

The specificity of CCP to RA was more than 96.0%. Citrullinated protein, as a target antigen, is involved in the pathogenesis of RA. The corresponding anti-CCP antibody has higher specificity for the early diagnosis of RA than traditional RF. Although the negative anti-CCP antibody can not completely rule out the possibility of RA disease, the positive anti-CCP antibody indicates a high possibility of developing into RA in the future. Because anti-CCP has the characteristics of high sensitivity, strong specificity and early diagnosis of RA patients, it has important clinical significance to grasp the effective treatment time window within 2 years.

• There was a significant correlation between CCP and the changes of disease, joint destruction and prognosis in patients with RA.

Anti-CCP antibodies can be secreted from synovium and peripheral blood lymphocytes of patients with RA, so it is related to the degree of destruction of bones and joints. Lnane et al reported that RA patients with positive anti-CCP antibody had high disease activity, severe joint erosion and severe functional destruction, which were significantly correlated with clinical disease activity indexes such as ESR, CRP and DAS28 scores.

• The combined detection of CCP and IgG-RF can greatly improve the specificity of diagnosis, and help to judge the disease and observe the curative effect.

At present, there is no single clinical test item for the detection of RA that can take into account both sensitivity and specificity. CCP combined with RF, the common immunological index of RA, is of more clinical significance for the diagnosis of RA. The combined detection of CCP and IgG-RF has high sensitivity and specificity in the diagnosis of RA, and can be used in the early diagnosis and prognosis evaluation of RA, which is helpful to improve the diagnosis of early RA patients with RF. It is a good index for early and accurate diagnosis of RA and excluding joint diseases caused by non-RA, especially for early RA patients with atypical clinical symptoms.

The examination of CCP antibody

CCP antibody is an ideal serological index for early diagnosis of RA. At present, CCP antibody is mainly detected by enzyme-linked immunosorbent assay (ELISA), fluorescence enzyme immunoassay (ELIA) and chemiluminescence enzyme immunoassay (CLEIA). CLEIA for the detection of CCP antibody is a determination method that uses enzyme-catalyzed chemiluminescence to convert the recorded photon number into the content of the detected substance. Compared with ELISA, it is characterized by completely automatic operation, wide determination range and less time, so it is the most popular detection method in clinic at present.

Conclusion

In summary, citrullination and anti-citrullinated peptide antibodies (ACPA) play a key role in causing inflammation in autoimmune diseases such as rheumatoid arthritis (RA). The anti-CCP detection is a relatively new assay, which can detect the presence of citrulline antibodies in blood. These autoantibodies are proteins produced by the immune system in response to citrulline-aware threats. The sooner you are diagnosed with anti-CCP positive rheumatoid arthritis, the sooner you start targeted treatment. Early detection can help patients maintain quality of life and prevent severe progression of rheumatoid arthritis.

References

1. Vossenaar, E. R., Zendman, A. J., & Van Venrooij, W. J. (2003). Citrullination, a possible functional link between susceptibility genes and rheumatoid arthritis. Arthritis Res Ther, 6(1), 1-5.
2. Reichert, S., Schlumberger, W., Dähnrich, C., Hornig, N., Altermann, W., Schaller, H. G., & Schulz, S. (2015). 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(1), 1-10.
3. Whiting, P. F., Smidt, N., Sterne, J. A., Harbord, R., Burton, A., Burke, M., ... & Dieppe, P. (2010). Systematic review: accuracy of anti–citrullinated peptide antibodies for diagnosing rheumatoid arthritis. Annals of internal medicine, 152(7), 456-464.
4. Rajalingam, S., Sakthiswary, R., & Hussein, H. (2017). Anti-citrullinated cyclic peptide antibody and functional disability are associated with poor sleep quality in rheumatoid arthritis. Archives of Rheumatology, 32(1), 15.