title: Thioredoxin as a biomarker for oxidative stress in patients with rheumatoid arthritis.
abstract: There is no doubt that oxidative stress occurs in patients with rheumatoid arthritis (RA) and play an important role in both inflammation and destruction of RA joints. Thioredoxin (TRX) is a ubiquitous redox-active protein and is known to be induced in several cells against oxidative stress and to be secreted extracellularly. To clarify whether plasma thioredoxin levels could be a marker for oxidative stress in patients with RA, we measured plasma TRX levels in patients with RA using a sensitive sandwich enzyme-linked immunosorbent assay (ELISA) and investigated its relationship to TRX concentrations in the inflammatory joints. We have found that the plasma TRX levels of RA patients were significantly higher than those of normal subjects (86.8 +/-54.1 ng/ml versus 38.6 +/-18.5 ng/ml, P<0.0001). The plasma levels were correlated with the disease activity of RA and also with serum C-reactive protein (CRP) values (P<0.01). The concentration of TRX in synovial fluid (SF) from RA was 353.3 +/- 220.1 ng/ml (mean +/- S.D.) which was significantly higher than that in SF from osteoarthritis patients (70.6 +/- 31.0 ng/ml, P<0.0001). The SF TRX concentration was significantly correlated with the number of leukocytes infiltrating in SF and with the serum CRP levels. The serum TRX levels were significantly positively correlated with the SF TRX concentrations in RA patients (P<0.05). By the histological examination for synovial tissue of RA patients, TRX was shown to be present on the surface of synovial lining layer as well as in the leukocytes.Moreover, urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage by endogenously generated oxygen radicals, was significantly higher in RA patients than in healthy subjects (11.55 +/- 4.71 versus 7.76 +/- 2.26 ng/mg creatinine, P<0.0001). Plasma TRX levels were significantly correlated with urinary excretion of 8-OHdG (P<0.005). We concluded that plasma TRX level is a new biomarker for the disease activity of RA and may reflect higher levels of oxidative stress in RA patients.
authors.affiliation: Department of Clinical Pathology and Immunology, Graduate School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuou-ku, Kobe, 650-0017, Hyogo, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Jikimoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nishikubo
authors.forename: Masahiro
authors.initials: M
authors.lastname: Koshiba
authors.forename: Sugayo
authors.initials: S
authors.lastname: Kanagawa
authors.forename: Sahoko
authors.initials: S
authors.lastname: Morinobu
authors.forename: Akio
authors.initials: A
authors.lastname: Morinobu
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Saura
authors.forename: Kosaku
authors.initials: K
authors.lastname: Mizuno
authors.forename: Shohei
authors.initials: S
authors.lastname: Kondo
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kumagai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood*; D015415:Biomarkers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D013879:Thioredoxins / Q000097:blood*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D013879:Thioredoxins