Rheumatoid Factor and Anti-CCP Antibodies as Diagnostic and Prognostic Biomarkers in Rheumatoid Arthritis: A Comprehensive Review

Abstract

Background: Rheumatoid arthritis is a long-standing autoimmune condition marked by ongoing inflammation of the synovial joints, progressive joint damage, and widespread systemic effects. Early diagnosis is essential to prevent irreversible disability. Of the various biomarkers currently in use, Rheumatoid Factor (RF) and Anti-Cyclic Citrullinated Peptide (Anti-CCP) antibodies remain the most commonly utilised. Over the past decade, Anti-CCP has emerged as a highly specific marker for RA, while RF continues to serve as a classical but less specific indicator.

Aim and Objective:  This review provides an updated and comprehensive comparative analysis of RF and Anti-CCP antibodies as diagnostic, predictive, and prognostic markers.

Material and Methods: A narrative review was carried out integrating various verified sources such as PubMed, Scopus, Google Scholar, and Embase databases. Studies published between 2015 and 2025 evaluating RF and Anti-CCP in RA diagnosis, prognosis, disease activity, and correlation with radiological or clinical outcomes were included. A total of 82 articles were screened, and 52 relevant studies were analyzed qualitatively.

Results: Anti-CCP exhibited a specificity of 91–98%, significantly higher than RF (70–85%). RF demonstrated higher sensitivity (75–85%) compared to Anti-CCP (60–75%) in early disease. Combined positivity of RF + Anti-CCP increased diagnostic accuracy to >95%. Anti-CCP positivity strongly correlated with radiographic progression, erosive disease, higher DAS28 scores, and poor functional outcomes. RF showed associations with disease severity but lacked prognostic consistency. Anti-CCP antibodies appeared even years before clinical onset, supporting their role as preclinical markers.

Conclusion: Anti-CCP is superior to RF in specificity, prognostic value, and prediction of erosive disease. RF retains utility as a sensitive screening marker. Combined testing improves diagnostic accuracy and enables early therapeutic interventions. Future research should focus on integrating novel biomarkers with RF and Anti-CCP for personalized RA management.