酸化ストレスと検査(4)

酸化ストレスと自己免疫

熊　谷　俊　一*1　直　本　拓　己*2　三　枝　　　淳*3
　　　　　　　　　　　　　　　　　　　　　　
Pathological Roles of Oxidative Stress
in Autoimmune Diseases

Shunichi KUMAGAI, MD*1, Takumi JIKIMOTO*2
and Jun SAEGUSA, MD*3

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 Sjogren'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.
[Rinsho Byori 51 : 126〜132, 2003]

*1Department of Biomedical Informatics, Graduate School of Medicine, Kobe University, Kobe 560-0017

【Key Words】oxidative stress(酸化ストレス)，antioxidant systems(抗酸化機構)，autoimmune diseases(自己免疫疾患)，thioredoxin(チオレドキシン)，rheumatoid arthritis(関節リウマチ)，Sjogren's syndrome(シェーグレン症候群)

*1神戸大学大学院医学系研究科生態情報医学，*2同　附属病院検査部(〒650-0017 神戸市中央区楠町7-5-2)
*3倉敷中央病院内分泌代謝・リウマチ内科(〒710-8602倉敷市美和1-1-1)

E-mail :kumagais@kobe-u.ac.jp