Abstract

Autoimmune disorders such as rheumatoid arthritis (RA) arise from a breakdown in immune tolerance, leading to 
chronic inflammation, autoantibody production, and progressive tissue destruction. Among these autoantibodies, 
rheumatoid factor (RF)-an immunoglobulin directed against the Fc region of IgG-serves not only as an important 
diagnostic biomarker but also as a mechanistic contributor to disease amplification and chronicity. Increasing 
evidence indicates that oxidative stress and redox imbalance are critical drivers of autoimmune activation, antigen 
modification, and RF production. Reactive oxygen species (ROS) generated by activated neutrophils, macrophages, 
and synovial fibroblasts can modulate antigen structure, enhance immunogenicity, and alter B-cell signalling 
dynamics, thereby creating a feed-forward loop of inflammation and autoantibody formation. However, the 
physiological redox system, including enzymatic and non-enzymatic antioxidants, serves as a counterbalance that 
can restrain excessive immune activation. Emerging research suggests that antioxidant molecules can influence 
B-cell tolerance, antigen processing, cytokine patterns, and Fc-receptor–mediated pathways linked to RF activity. 
Despite this, the therapeutic potential of antioxidants remains underinvestigated and poorly integrated into 
current treatment paradigms for autoimmune diseases. This review explores the redox–immune interface in 
autoimmune pathology, elucidates molecular mechanisms linking oxidative stress to RF production and 
pathogenicity, and critically evaluates the potential of antioxidant strategies in modulating these pathways. We 
highlight key research gaps and propose future directions for incorporating redox-based interventions into 
comprehensive autoimmune disease management.