Clinical Applications of Cell-free DNA in Rheumatoid Arthritis: Molecular Diagnosis, Monitoring, and Prognosis

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive synovial inflammation and joint destruction.Existing diagnostic biomarkers, such as rheumatoid factor and anti-citrullinated protein antibodies (ACPA) lack sufficient sensitivity and specificity, highlighting the need for new biomarkers.Cell-free DNA (cfDNA), which is released into body fluids during apoptosis, necrosis, and neutrophil extracellular trap formation, has been studied as a biomarker in various clinical contexts, including oncology and transplantation.Recent studies have explored their role in RA-related autoimmunity.Several reports have demonstrated significant increases in cfDNA levels in the synovial fluid of patients with RA, showing strong correlations with disease activity score, erythrocyte sedimentation rate, and C-reactive protein.Furthermore, cfDNA features, such as fragment size distribution, methylation patterns, and mitochondrial DNA enrichment, have been implicated in the pathophysiology, diagnosis, and prognosis of RA.To enhance its clinical utility, integrated multi-omics approaches that incorporate cfDNA analysis are required.Ultimately, cfDNA holds promise as a non-invasive and repeatable biomarker, offering the potential to develop precise on-site platforms for real-time diagnosis, monitoring, and prognosis of RA.