Anti-citrullinated procollagen C-endopeptidase enhancer antibody: a potential biomarker for seronegative rheumatoid arthritis

Although with great advances, the biomarkers used in the diagnosis of rheumatoid arthritis (RA) are still challenging, especially in seronegative RA. Recently, procollagen C-endopeptidase enhancer (PCOLCE) was revealed as a potential autoantigen of seronegative RA by our group. This study aimed to further analyze the B cell autoantigenic epitopes of PCOLCE and the diagnostic value of its antibody in seronegative RA. The B cell epitopes of PCOLCE were elucidated by the Immune Epitope Database and molecular mimicry analyses. The anti-citrullinated PCOLCE271-284 antibody (anti-PCOLCE) was tested in a total of 612 serum samples including RA patients, healthy controls, and patients with other rheumatic diseases. The diagnostic value of anti-PCOLCE in RA, especially for seronegative RA, was evaluated by ROC curve, sensitivity, and specificity. Anti-PCOLCE in combination with anti-CCP for RA diagnosis was also demonstrated. The correlations of anti-PCOLCE with RA patient features were further analyzed. Anti-PCOLCE was significantly elevated in RA serums with a sensitivity of 51.53% and specificity of 93.60%. More importantly, anti-PCOLCE had a favorable diagnostic value in seronegative RA, revealing a positive rate of 40.00% in anti-CCP negative RA, 38.76% in RF negative RA, and 36.46% in anti-CCP and RF negative RA. The combination of anti-PCOLCE with anti-CCP demonstrated a high sensitivity of 82.14% and specificity of 90.21%. Anti-PCOLCE also has good diagnostic value in RA patients with normal inflammatory factors and early RA. Moreover, anti-PCOLCE was positively correlated with CRP, anti-CCP, and RF. Anti-PCOLCE could serve as a novel biomarker for RA, especially for seronegative RA.