[Pathological roles of oxidative stress in autoimmune diseases]

Autoimmune diseases are complex diseases in which both genetic and environmental factors are involved. Excessive oxidative stress is thought to have an important role in the pathogenesis of autoimmune diseases by enhancing the inflammation, inducing apoptotic cell death, and breaking down the immunological tolerance. When the state of oxidative stress was investigated in patients with rheumatoid arthritis(RA), systemic lupus erythematosus(SLE), and Sjögren's syndrome(SS) by oxidative stress profile(OSP), most subjects were in excessive oxidative stress or in defective antioxidant potentials. The thioredoxin(TRX) level in peripheral blood was significantly higher in these patients than in healthy subjects. Urinary excretion of 8-hydroxy-guanosine was also significantly increased in these patients compared with healthy subjects. We have proven that oxidative stress as well as UV irradiation induced the expression of SS-A/Ro52 autoantigen on the cell surface of keratinocytes. Oxidative stress not only injures the cellular components but also induces cellular responses, including apoptosis and gene activation. We also identified that GSTM1 null genotype was a candidate gene for susceptibility to SS and was associated with SS-A/Ro autoantibody production. In the synovial fluid of RA patients, TRX was abundantly detected and was produced in the lining layer of synovial tissue, indicating that TRX might protect synovial tissue from oxidative stress. Infections, UV irradiation, coldness, and emotional stress have been clinically well known as developing and exacerbating factors for autoimmune diseases. These environmental factors are closely related to oxidative stress. It is very important to develop reliable test methods to detect the state of oxidative stress and antioxidants.