Targeting the ROS-ferroptosis axis: A clinical perspective on oxidative stress management in systemic lupus erythematosus.

Abstract

Systemic lupus erythematosus (SLE) is a classic autoimmune condition marked by inflammation in multiple organs and a malfunctioning immune system. Despite advances in immunosuppressive therapies, patients frequently experience relapses, organ damage, and significant quality-of-life impairment. Recent findings indicate that ferroptosis, a form of regulated cell death dependent on iron, has a substantial impact on the progression of lupus. However, the precise molecular interplay between ROS generation, iron metabolism dysregulation, and immune cell dysfunction in SLE remains incompletely understood. This review analyzes the ROS-ferroptosis axis in SLE, highlighting its role in promoting pathological immune responses and worsening tissue injury. It also discusses targeted therapies like iron chelators and GPX4 agonists, which show promise in preclinical models and early trials, identifies actionable targets, evaluates their translational potential for precision therapies, and bridges preclinical mechanisms with clinical applications to address unmet SLE management needs.