Thioredoxin as a biomarker for oxidative stress in patients with rheumatoid arthritis
Thioredoxin as a biomarker for oxidative stress in patients with rheumatoid arthritis
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DOI：
10.1016/s0161-5890(01)00113-4
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发表时间：
2002-02-01
影响因子：
3.6
通讯作者：
Kumagai, S
中科院分区：
文献类型：
--
作者：
Jikimoto, T;Nishikubo, Y;Kumagai, S
毫无疑问，氧化应激发生在类风湿关节炎（RA）患者中，并在RA关节的炎症和破坏中发挥重要作用。硫氧还蛋白（TRX）是一种普遍存在的氧化还原活性蛋白，已知其在多种细胞中被诱导以对抗氧化应激并被分泌到细胞外。为了阐明血浆硫氧还蛋白水平是否可以作为RA患者氧化应激的标志物，我们采用双抗体夹心酶联免疫吸附法（ELISA）测定了RA患者血浆TRX水平，并探讨了其与炎性关节中TRX浓度的关系，发现RA患者血浆TRX水平显著高于正常人（86.8 +/- 54.1 ng/ml对比38.61 +/- 18.5 ng/ml，P < 0.0001）。RA患者血浆CRP水平与病情活动度及血清C反应蛋白（CRP）水平呈正相关（P < 0.01）。RA患者滑液中TRX浓度为353.3 ± 220.1 n/ml（平均S.D.）。与骨关节炎患者血清中的70.6 ± 31.0ng/ml相比，差异有显著性（P < 0.0001）。SF TRX浓度与SF中浸润的白细胞数量和血清CRP水平显著相关。RA患者血清TRX水平与SFTRX水平呈显著正相关（P < 0.05）。通过对RA患者滑膜组织的组织学检查，显示TRX存在于滑膜衬里层表面以及白细胞中，并且尿中排出的8-羟基-2 '-脱氧鸟苷（8-OHdG）是内源性氧自由基氧化DNA损伤的生物标志物，RA患者的肌酐水平显著高于健康受试者（11.55 ± 4.71 vs 7.76 ± 2.26 ng/mg肌酐，P < 0.0001）。血浆TRX水平与尿8-OHdG排泄量呈显著正相关（P < 0.005）。我们的结论是，血浆TRX水平是一个新的生物标志物的疾病活动的RA，并可能反映较高水平的氧化应激在RA患者。0 2002爱思唯尔科技有限公司版权所有。
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 38.61 +/- 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 n/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 SFTRX 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. 0 2002 Elsevier Science Ltd. All rights reserved.