Enrichment of reverted genes.

It is well documented that patients affected by rheumatoid arthritis (RA) have distinct susceptibility to the different biologic DMARDs available on the market, probably because of the many facets of the disease. Monocytes are deeply involved in the pathogenesis of RA and we therefore evaluated and compared the transcriptomic profile of monocytes isolated from patients on treatment with methotrexate alone or in combination with tocilizumab, anti-TNFα or abatacept and from healthy donors. Whole-genome transcriptomics yielded a list of regulated genes by Rank Product statistics and DAVID was then used for functional annotation enrichment analysis. Last, data were validated by qRT-PCR. Abatacept, tocilizumab and anti-TNFa cohorts were separately compared with methotrexate, leading to the identification of 78, 6, and 436 differentially expressed genes, respectively. The upper-most ranked genes were related to inflammatory processes and immune responses. Such an approach draws the genomic profile of monocytes in treated RA patients and lays the basis for finding gene signature for tailored therapeutic choices.

已有充分文献证实，类风湿关节炎（rheumatoid arthritis, RA）患者对市场上在售的各类生物改善病情抗风湿药（biologic DMARDs）存在显著不同的敏感性，这可能与该疾病的多维度病理特征相关。单核细胞深度参与类风湿关节炎的发病机制，因此本研究对接受单一甲氨蝶呤（methotrexate）治疗、或联合托珠单抗（tocilizumab）、抗TNFα或阿巴西普（abatacept）治疗的RA患者，以及健康供者的分离单核细胞转录组谱进行了评估与比较。本研究通过全基因组转录组学结合秩积（Rank Product）统计法筛选得到差异调控基因列表，随后采用DAVID数据库开展功能注释富集分析，最终通过实时定量聚合酶链式反应（quantitative Real-Time Polymerase Chain Reaction, qRT-PCR）对转录组数据进行验证。分别将阿巴西普、托珠单抗与抗TNFα治疗组与甲氨蝶呤单药组进行对照比较，分别鉴定得到78个、6个及436个差异表达基因。排名靠前的差异基因主要与炎症过程及免疫应答相关。本研究通过上述方法明确了接受治疗的RA患者单核细胞的基因组特征，并为探寻可指导个体化治疗选择的基因特征奠定了研究基础。