Citrullinated Antigens With Multiple Citrulline Similar Motif In The Diagnosis Of Rheumatoid Arthritis:A Preliminary Single-Center Study

Objectives:The present study aimed to detect the level of serum citrullinated antigen in patients with rheumatoid arthritis（RA）and evaluate the application of serum citrullinated antigen as a novel biomarker in early diagnosis of RA.Methods:1.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.2.263 RA patients,48 other arthritis patients（26 spondyloarthritis,21 osteoarthritis,1 juvenile idiopathic arthritis）and 41 healthy subjects were included in this study.citrullinated antigens against anti-MCSM antibody was detected by enzyme linked immunosorbent assay（ELISA）and the sensitivity and specificity of serum citrullinated antigen with MCSM in the diagnosis of RA was analyzed.Moreover,the correlation analysis was used between anti-cyclic citrullinated peptide（CCP）antibodies and part of clinical data in RA patients.Results:1.263 out of the RA patients（93.2%）and 5 out of the other arthritis（10.4%,including 3 ankylosing spondylitis,1 osteoarthritis,and 1 undifferentiated spondyloarthritis）were positive for citrullinated antigens with MCSM.All healthy controls were negative.2.ROC curve analysis was performed for anti-CCP and citrullinated antigens with MCSM.The diagnostic sensitivity for anti-CCP and MCSM was 84.4%and 93.2%,respectively,while the specificity was 100%and 94.4%,respectively.The area under the curve（AUC）values were 0.922（95%CI:0.894-0.950）for anti-CCP and 0.938（95%CI:0.905-0.971）for MCSM.Combined MCSM and anti-CCP detection had the highest AUC 0.961（95%CI:0.942-0.981）.3.Among anti CCP antibody negative patients,there was significant difference in RF between MCSM positive and negative patients（P<0.05）,but there was no significant difference in ESR,C-reactive protein,age and course of disease.Conclusions:Serum citrullinated antigen with MCSM and anti-CCP antibody detection have high consistency,and the sensitivity to the diagnosis of RA is higher than that of anti-CCP antibody,which is helpful for early diagnosis of RA patients with negative anti-CCP antibody and can be used as an effective biomarker for RA diagnosis.