Gene expression profiling of relevant biomarkers for treatment evaluation in multiple sclerosis
Gene expression profiling of relevant biomarkers for treatment evaluation in multiple sclerosis
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DOI：
10.1016/j.jneuroim.2004.03.004
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发表时间：
2004-07-01
影响因子：
3.3
通讯作者：
Zhang, JWZ
中科院分区：
文献类型：
--
作者：
Hong, J;Zang, YCQ;Zhang, JWZ
多发性硬化症（MS）被认为与炎症过程中产生的一系列临床相关生物标志物相关。在这项研究中，开发了一种新的基因表达谱技术，并对其进行了表征，以定量测量34个基因的表达谱，这些基因是根据它们在炎症中的作用以及它们对当前MS治疗药物β -干扰素（IFN）和醋酸格拉替雷默（GA）的调节易感性而选择的。通过对MS患者和对照组外周血单个核细胞（PBMC）的体外和离体分析，评估了该技术的潜在临床应用。干扰素诱导基因在体外β - ifn处理后普遍上调，而其他选定的编码细胞因子和与T细胞运输、活化和凋亡相关的分子的基因的表达则受到不同程度的影响。β - ifn和GA对所选基因的表达表现出独特的调控作用。在一项自我配对研究中，通过比较β - ifn或GA治疗在同一患者中引起的特异性变化，以及在一项小组研究中通过测量治疗组与未治疗组的特异性特征，通过对PBMC标本的离体分析，发现了β - ifn和GA的类似调节特性。此外，基于血清抗体对已知的β - ifn对PBMC的调节特性的阻断作用，该技术可作为检测β - ifn中和抗体的一种简单而敏感的方法。这些发现为β - ifn和GA的免疫调节特性提供了重要信息，并支持该技术在检测中和抗体（NAB）和评估MS患者治疗反应方面的潜在临床应用。(C) 2004 Elsevier B.V.版权所有
Multiple sclerosis (MS) is thought to correlate with an array of clinically relevant biomarkers produced during inflammatory process. In this study, a novel gene expression profiling technology was developed and characterized to quantitatively measure the expression profiles of 34 genes selected based on their role in inflammation and their susceptibility to regulation by current MS treatment agents, beta-interferon (IFN) and glatiramer acetate (GA). Potential clinical applications of the technology were evaluated by in vitro and ex vivo analyses in peripheral blood mononuclear cells (PBMC) obtained from MS patients and controls. Interferon-inducible genes were universally upregulated after in vitro treatment with beta-IFN while the expression of other selected genes encoding cytokines and molecules related to T cell trafficking, activation and apoptosis was variably affected. Beta-IFN and GA exhibited distinctive and characteristic regulatory effects on the expression of the selected genes. Similar regulatory properties of beta-IFN and GA were seen by ex vivo analysis of PBMC specimens in a self-paired study by comparing specific changes induced by beta-IFN or GA treatment in the same patients as well as in a group study by measuring specific profiles in treatment groups compared with an untreated group. Furthermore, the technology served as a simple and sensitive assay for detection of beta-IFN neutralizing antibody based on the blocking effect of serum antibodies on the known regulatory properties of beta-IFN on PBMC. The findings provide important information on the immunoregulatory properties of beta-IFN and GA and support potential clinical applications of this technology in detection of neutralizing antibody (NAB) and evaluation of treatment responses in MS patients. (C) 2004 Elsevier B.V. All rights reserved.