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托珠单抗(一种抗白细胞介素-6 受体抗体)治疗类风湿关节炎患者的血清蛋白质组分析。

Serum proteome analysis in patients with rheumatoid arthritis receiving therapy with tocilizumab: an anti-interleukin-6 receptor antibody.

机构信息

Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu-shi, Chiba 279-0021, Japan.

出版信息

Biomed Res Int. 2013;2013:607137. doi: 10.1155/2013/607137. Epub 2013 Aug 22.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disorder of the synovial membrane that results in the destruction of bone and cartilage in affected joints. Tocilizumab is a biological agent and an anti-interleukin-6 (IL-6) receptor monoclonal antibody that blocks IL-6-mediated inflammatory processes in RA patients. In order to identify novel disease-related proteins and candidate biomarkers, we analyzed the changes in the serum proteome profiles of patients with RA who were treated with tocilizumab. Serum samples were collected from the RA patients before and after tocilizumab treatment. Following immunodepletion of major proteins, the proteins were digested and labeled with isobaric tag, iTRAQ reagent. The proteins were identified and quantified using liquid chromatography-tandem mass spectrometry. Among a total of 311 proteins identified, seven were decreased and 16 were increased by tocilizumab treatment. Although some of the proteins are known to be related to RA, several are currently unknown with respect to their relationship to RA and may be involved in the development of this disease. This study is the first to perform a comparative serum proteomic analysis of RA patients treated with tocilizumab. Our results may contribute to the identification of novel disease-related proteins and enhance the understanding of the pathogenesis of RA.

摘要

类风湿关节炎(RA)是一种慢性炎症性滑膜疾病,可导致受影响关节的骨和软骨破坏。托珠单抗是一种生物制剂和抗白细胞介素-6(IL-6)受体单克隆抗体,可阻断 RA 患者的 IL-6 介导的炎症过程。为了鉴定新的疾病相关蛋白和候选生物标志物,我们分析了接受托珠单抗治疗的 RA 患者血清蛋白质组谱的变化。在托珠单抗治疗前后收集 RA 患者的血清样本。在用免疫沉淀法去除主要蛋白质后,用等重同位素标记相对和绝对定量试剂(iTRAQ)对蛋白质进行消化和标记。使用液相色谱-串联质谱法对蛋白质进行鉴定和定量。在总共鉴定出的 311 种蛋白质中,有 7 种被托珠单抗治疗降低,16 种被托珠单抗治疗增加。尽管其中一些蛋白质已知与 RA 有关,但有几个目前尚不清楚与 RA 的关系,可能与该疾病的发展有关。本研究首次对接受托珠单抗治疗的 RA 患者进行了比较血清蛋白质组学分析。我们的结果可能有助于鉴定新的疾病相关蛋白,并增强对 RA 发病机制的理解。

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