Role of free radicals in autoimmune diseases

Free radicals are highly reactive molecules that are unstable and have extremely short life periods. They are derived from either oxygen (reactive oxygen species, ROS) or nitrogen (reactive nitrogen species, RNS) in mitochondria, plasma membrane, and endoplasmic reticulum membrane due to oxidative stress and damage. ROS/RNS are physiologically useful at low concentration and are responsible for the activation of redox-sensitive signaling pathways, phagocytosis of infected cells, and removal of abnormal and aging cells. The endogenous sources of ROS are the electron transport chain, respiratory burst of phagocytes, and oxidation of lipids. These radicals react with biomolecules such as DNA, proteins, and lipids and may cause pathophysiological conditions such as autoimmunity, carcinogenesis, and neurodegenerative diseases. ROS are known to cause strand breaks, base damage, and conformational changes in DNA leading to the generation of neoepitopes. ROS-modified DNA may be one of the factors responsible for autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). ROS also appear to play a critical role in RA, a systemic autoimmune disease of the joints known as inflammatory arthritis (IA). The role of ROS in autoimmune response remains complex and they have been implicated in the initiation, generation, and amplification of novel epitopes.