Work

Association Between Anti-cyclic Citrullinated Protein Antibodies and Extra-articular Manifestations in Rheumatoid Arthritis

Year: 2026

Type: article

Abstract: Background: Anti-cyclic citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are established serological markers in rheumatoid arthritis (RA). However, their specific roles in the development of extra-articular manifestations (EAMs) remain a subject of debate. Objectives: This study aimed to quantitatively evaluate ACPA and RF titers and determine their predictive value for specific EAMs, particularly rheumatoid vasculitis (RV) and interstitial lung disease (ILD). Design: This research was designed as a retrospective cross-sectional study. Methods: We analyzed clinical data from 205 patients with RA, categorized into an RA control group (n = 129) and an RA-EAM group (n = 76). Serum ACPA and RF titers were measured using a second-generation chemiluminescent enzyme immunoassay. To validate the findings, a post hoc power analysis was conducted. Receiver operating characteristic (ROC) curves were generated to determine optimal ACPA cutoff values for predicting RV and ILD. Results: Serum ACPA titers, but not RF titers, were significantly elevated in patients with ILD and RV compared with those without EAMs ( P < .01). To evaluate the diagnostic utility of serum ACPA titers, ROC curve analysis was performed. Receiver operating characteristic curve analysis showed that ACPA had moderate discriminative ability for identifying RV (AUC = 0.755; 95% CI, 0.61-0.88). The optimal cutoff determined by Youden’s index was 120 U/mL (sensitivity 90.0%, specificity 59.7%). For ILD, the AUC was 0.693 (95% CI, 0.59-0.78), with an optimal cutoff value of 42 U/mL (sensitivity 85.0%, specificity 46.5%). ACPA levels in patients with other EAMs did not differ significantly from controls. Conclusion: Our results demonstrated that serum ACPA levels were significantly higher in patients with RA-associated ILD and RV compared with those without systemic involvement. Notably, this association was not observed for RF titers. These findings suggest that high-titer ACPAs may serve as a more specific immunological marker for these severe complications than traditional RF. Registration: Not applicable.

Source: Clinical Medicine Insights Arthritis and Musculoskeletal Disorders

DOI: 10.1177/11795441261497736