A new pattern of citrullinated peptides improves the sensitivity for diagnosing rheumatoid arthritis

• Published in: Clinical biochemistry Vol. 105-106; pp. 87 - 93
• Main Authors: Ru, Zhiwei, Zhang, Hongbin, Huang, Xiaoyan, Lou, Jianrong, Liao, Jun, Chen, Zhu, Yang, Xiang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2022
• Subjects: Anti-citrullinated protein/peptide antibody (ACPA); Cyclic citrullinated peptides (CCP); Multiple citrulline-similar motifs (MCSMs); Rheumatoid arthritis (RA); Rheumatoid arthritis (RA); Anti-citrullinated protein/peptide antibody (ACPA); Multiple citrulline-similar motifs (MCSMs); Cyclic citrullinated peptides (CCP)
• ISSN: 0009-9120; 1873-2933
• DOI: 10.1016/j.clinbiochem.2022.04.002

Anti-citrullinated protein antibody (ACPA) is found almost exclusively in patients with rheumatoid arthritis (RA). Commercial cyclic citrullinated peptide (CCP) assays that target ACPAs yield specificities as high as 95% for RA diagnoses, but their sensitivities only reach 50–70%. To improve the sensitivity of the CCP assay, a new pattern of citrullinated peptide was identified and named the MCSM (multiple citrulline-similar motif). The MCSM comprised a citrulline core surrounded by citrulline-similar amino acids. A series of peptides with or without the MCSM was synthesized to evaluate the function of the citrulline core and citrulline-similar amino acids. These peptides were used in the enzyme-linked immunosorbent assay to compare samples from 94 RA patients, 117 non-RA patients and 116 healthy subjects. Additionally, the MCSM assay was compared with a commercial CCP assay. When the cutoff value was set at 0.274, the sensitivity and specificity of the MCSM assay were 79.6% and 96.6%, respectively. When one citrulline was substituted in the citrulline core, the sensitivity of the assay decreased from 79.6% to 61%. If all three citrulline-similar amino acids were substituted in the backbone, the sensitivity of the MCSM assay decreased from 79.6% to 58.5%. The coincidence rate of the MCSM assay to the commercial CCP assay was 97.6%. The citrulline core and citrulline-similar amino acids are crucial components of the MCSM pattern. This new MCSM assay could be used to diagnose RA.