Epigenetic modifications of immune cells in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by synovial inflammation, joint destruction, and systemic features. Dysregulated immune cells-particularly T cells, B cells, and macrophages-drive its onset and progression. Epigenetic mechanisms, including DNA methylation, histone modifications, RNA editing, and non-coding RNAs, critically shape immune cell activation, differentiation, and effector functions, perpetuating autoimmunity and chronic inflammation.

Although individual epigenetic changes in RA have been widely studied, an integrated overview connecting these alterations to disease pathogenesis and clinical application is lacking. This review aims to synthesize current knowledge on how epigenetic modifications affect key immune populations in RA, evaluate their potential as biomarkers for diagnosis and prognosis, and discuss future directions for precision epigenetic therapies.

In RA, T cells show locus-specific hypomethylation and lncRNA-mediated regulation that boost inflammatory cytokine production. Macrophages undergo histone modification changes and altered RNA editing that amplify inflammation. B cells exhibit abnormal DNA methylation and microRNA profiles promoting autoantibody production. Together, these processes form a self-sustaining loop of immune activation. Clinically, epigenetic profiles may aid early detection and patient stratification. Targeting epigenetic enzymes and RNA-based therapies is promising but faces challenges in cell specificity, delivery, and variability.

Advances in epigenetics could enable personalized RA management. Integrative multi-omics and cell-specific interventions may restore immune balance, control inflammation, and prevent damage. Overcoming barriers to targeted delivery and clinical translation will be key for precision epigenetic therapies in RA.