Citrullinated Antigens with Multiple Citrulline Similar Motif in the Diagnosis of Rheumatoid Arthritis: A Preliminary Single-Center Study

Zhu Chen,Xiang Yang,Weiting Fang,Jianrong Lou,Yi Qin,Yin-Zhao Jin,Yan Yang

doi:10.1155/2021/1891519

Abstract

The presence of anti-citrullinated protein antibodies (ACPAs) in the serum is one of the immunological features of rheumatoid arthritis (RA). Anti-cyclic citrullinated peptide (CCP) assay has been widely used in clinic for the diagnosis of RA. However, up to 40% of RA patients are anti-CCP negative and the diagnostic sensitivity in this population needs to be improved for better clinical management. In this study, peptides with Multiple Citrulline Similar Motif (MCSM) were synthesized and a new ELISA system, which we called RA_CP, was developed to detect citrullinated antigens with MCSM present in the serum. 106 RA,48 other arthritis patients and 41 sex- and age-matched healthy controls (HCs) were included in this study. Patients with RA have a significantly higher amount of citrullinated antigens with MCSM than other arthritis patients and HCs. RA patients with positive anti-CCP are also MCSM positive, whereas 75% anti-CCP negative patients are positive for MCSM. The diagnostic sensitivity for anti-CCP and MCSM was 81.1% and 95.3%, while the specificity was 100% and 94.4%, respectively. ROC curve analyses showed that the area under the curve (AUC) values were 0.906 (95% CI: 0.860-0.951) for anti-CCP and 0.948 (95% CI: 0.912-0.985) for MCSM while the combination of MCSM and anti-CCP test has the highest AUC (0.971, 95% CI: 0.946–0.996). Our results suggest that detection of citrullinated antigens with MCSM has improved sensitivity compared with anti-CCP assay and could serve as a biomarker in diagnosis of RA patients.

Highlights

Rheumatoid arthritis (RA) is a chronic autoimmunemediated inflammatory disease which mainly affects small to medium joints and remains one of the leading courses of disability in western countries [1]
Receiver operating characteristic (ROC) curve analyses showed that the area under the curve (AUC) values were 0.906 for anti-cyclic citrullinated peptide (CCP) and 0.948 for Multiple Citrulline Similar Motif (MCSM) while the combination of MCSM and anti-CCP test has the highest AUC (0.971, 95% CI: 0.946–0.996)
Our results suggest that detection of citrullinated antigens with MCSM has improved sensitivity compared with anti-CCP assay and could serve as a biomarker in diagnosis of RA patients

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmunemediated inflammatory disease which mainly affects small to medium joints and remains one of the leading courses of disability in western countries [1]. Anti-cyclic citrullinated peptide (CCP) detected by ELISA has been introduced and widely used in clinic, Journal of Immunology Research serving as an important biomarker for diagnosis of RA [8]. Up to 40% of RA patients are anti-CCP negative and the diagnostic sensitivity in this population needs to be improved for better clinical management [9, 10]. Considering antigens normally emerge earlier than antibodies, we hypothesize it would be promising to detect citrullinated antigens for early diagnosis of RA patients. A new ELISA system, which we called RA_CP, was developed to detect citrullinated antigens with MCSM present in serum of RA patients. We further examined the sensitivity and specificity of citrullinated antigens with MCSM and compared with conventional anti-CCP test to evaluate its potential value for application in clinic

Methods

Results

Conclusion