Identification of markers of responsiveness in rheumatoid arthritis patients. Homo sapiens

Despite the increasing of available drugs in RA, the overall rate of non response is 30 to 40% of treated patients. To optimize the drug prescription and better elaborate the therapeutic strategies, gene profiling in PBMCs was used to predict the responsiveness to anakinra. Thirty two patients treated by anakinra (100mg/day s.c.) and méthotrexate, were categorized as responders whenever a change of Disease Activity Score 28 > 1.2 was obtained at 3 months. Blood from treated patients was collected at baseline. In 7 responders and 7 non responders, 51 mRNAs identified by microarray were expressed as a function of the response to treatment and an unsupervised hierarchical clustering perfectly separated responders from non responders. Keywords: anakinra effect Overall design: PBMC then RNA were extracted from blood samples of 7 anakinra responders, 7 anakinra non responders and 1 pool of healthy subjects used as control. Each sample was hybridized twice in different nylon membrane. The control sample was hybridized twice in each nylon membrane.

尽管类风湿关节炎（Rheumatoid Arthritis, RA）的获批治疗药物日益增多，但接受规范治疗的患者中，无应答率整体可达30%至40%。为优化药物处方并完善治疗策略，本研究通过对外周血单个核细胞（Peripheral Blood Mononuclear Cells, PBMC）进行基因表达谱分析，预测患者对阿那白滞素（Anakinra）的治疗应答情况。本研究共纳入32例接受阿那白滞素（100mg/日皮下注射）联合甲氨蝶呤（Methotrexate）治疗的RA患者，若患者在治疗3个月时的28关节疾病活动度评分（Disease Activity Score 28, DAS28）变化量＞1.2，则将其归类为治疗应答者。所有入组患者均于基线阶段采集外周血样本。在7例应答者与7例无应答者中，经微阵列芯片（microarray）鉴定出的51个mRNA的表达水平与治疗应答情况显著相关，且无监督层级聚类（unsupervised hierarchical clustering）可完全将应答者与无应答者区分开来。关键词：阿那白滞素作用 研究设计概述：从7例阿那白滞素应答者、7例阿那白滞素无应答者的外周血样本中提取外周血单个核细胞，进而分离总RNA；同时设置1份健康受试者混合样本作为对照。每个样本均在两张不同的尼龙膜上完成两轮杂交；对照样本则在每张尼龙膜上均进行两轮杂交。