Gene expression in PBMC from Multiple Sclerosis patients undergoing interferon beta therapy.

We studied the gene expression patterns in PBMC from relapsing remitting MS patients undergoing weekly IFN-ß-1a therapy. On the basis of two fold changes in expression levels and statistical analyses we selected a diagnostic set of 137 genes that were differentially expressed between pretreatment and IFN-ß-1a-treated MS patients. Some these 137 genes may provide the basis for lack of IFN-ß-1a response. Keywords: Drug response to Interferon beta therapy in Multiple Sclerosis patients. We studied five RRMS patients with ages ranging from 32 to 46 years naïve to IFN-ß-1a therapy at the outset of the trial. The pretreatment and acute peripheral blood samples respectively were drawn the day before and the day after the start of the therapy. The chronic samples were drawn one day before the weekly treatment regimen approximately six months following the initiation of therapy. Mononuclear cells were purified from the fresh peripheral blood specimens using Ficoll-Paque density gradient separation. RNA was isolated from the PBMC using the Qiagen column purification procedure (Qiagen, Valencia, CA). We utilized the CodeLink Expression Bioarrays for the analysis of gene expression in PBMC.

我们对接受每周一次干扰素β-1a（IFN-ß-1a）治疗的复发缓解型多发性硬化（relapsing remitting multiple sclerosis, RRMS）患者的外周血单个核细胞（peripheral blood mononuclear cell, PBMC）基因表达模式展开了研究。基于表达水平2倍差异及统计学分析结果，我们筛选出137个在治疗前与接受干扰素β-1a治疗的多发性硬化患者间存在差异表达的基因，构建诊断特征基因集。上述137个基因中，部分可能可作为干扰素β-1a治疗应答缺失的潜在依据。关键词：多发性硬化患者对干扰素β治疗的药物应答。本研究纳入5名年龄介于32至46岁、入组初始时未接受过干扰素β-1a治疗的复发缓解型多发性硬化患者。分别于治疗开始前1天及治疗开始后1天采集患者外周血，作为预处理样本及急性期样本；在治疗启动约6个月后，于每周治疗方案实施前1天采集慢性期外周血样本。采用Ficoll-Paque密度梯度离心法从新鲜外周血标本中纯化单个核细胞，使用Qiagen柱纯化法（Qiagen，美国加利福尼亚州巴伦西亚）从外周血单个核细胞中提取RNA，并通过CodeLink表达生物芯片完成外周血单个核细胞的基因表达分析。