Ferroptosis in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently emerged as a potential contributor to RA pathogenesis.

A systematic literature review was conducted to explore the mechanisms of ferroptosis in RA, focusing on iron metabolism dysregulation, oxidative stress, and immune cell dysfunction. Databases including PubMed, Embase, and Web of Science were searched for relevant studies.

RA patients exhibit paradoxical iron distribution, with systemic deficiency but synovial overload, promoting ferroptosis. Key findings include: (1) Iron accumulation and lipid peroxidation exacerbate synovial inflammation; (2) Ferroptosis differentially affects immune cells (M1/M2 macrophages, T cells) and fibroblast-like synoviocytes (FLS); (3) Antioxidant defenses (GPX4) are impaired in RA, while some disease-modifying drugs (leflunomide, sulfasalazine) may modulate ferroptosis.

Ferroptosis plays a critical role in RA progression by disrupting synovial homeostasis. Targeting ferroptosis pathways offers promising therapeutic potential, though further research is needed to clarify cell-specific effects and optimize interventions.