BACKGROUND Abatacept (ABA) is a biological disease-modifying antirheumatic drug (bDMARD) for rheumatoid arthritis (RA). The aim of this study was to identify molecules that are associated with therapeutic responses to ABA in patients with RA. METHODS Peripheral blood was collected using a PAX gene Blood RNA kit from 45 bDMARD-naïve patients with RA at baseline and at 6 months after the initiation of ABA treatment. Gene expression levels of responders (n = 27) and non-responders (n = 8) to ABA treatment among patients with RA at baseline were compared using a microarray. The gene expression levels were confirmed using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS Gene expression analysis revealed that the expression levels of 218 genes were significantly higher and those of 392 genes were significantly lower in the responders compared to the non-responders. Gene ontology analysis of the 218 genes identified "response to type I interferon (IFN)" with 24 type I IFN-related genes. RT-qPCR confirmed that there was a strong correlation between the score calculated using the 24 genes and that using OAS3, MX1, and IFIT3 (type I IFN score) (rho with the type I IFN score 0.981); the type I IFN score was significantly decreased after treatment with ABA in the responders (p < 0.05), but not in the non-responders. The receiver operating characteristic curve analysis of the type I IFN score showed that sensitivity, specificity, and AUC (95% confidence interval) for the responders were 0.82, 1.00, and 0.92 (0.82-1.00), respectively. Further, RT-qPCR demonstrated higher expression levels of BATF2, LAMP3, CD83, CLEC4A, IDO1, IRF7, STAT1, STAT2, and TNFSF10 in the responders, all of which are dendritic cell-related genes or type I IFN-related genes with significant biological implications. CONCLUSION Type I IFN score and expression levels of the nine genes may serve as novel biomarkers associated with a clinical response to ABA in patients with RA.

中文翻译：

---

鉴定与类风湿关节炎患者对abatacept反应相关的分子。

背景技术阿巴西普（ABA）是一种用于风湿性关节炎（RA）的生物疾病改良抗风湿药（bDMARD）。这项研究的目的是鉴定与RA患者对ABA的治疗反应相关的分子。方法在基线和开始ABA治疗后6个月，使用PAX基因Blood RNA试剂盒从45例bDMARD初治的RA患者中收集外周血。使用微阵列比较了基线时RA患者中ABA治疗的应答​​者（n = 27）和非应答者（n = 8）的基因表达水平。使用实时定量聚合酶链反应（RT-qPCR）确认基因表达水平。结果基因表达分析表明，与非应答者相比，应答者中218个基因的表达水平显着较高，而392个基因的表达水平显着较低。218个基因的基因本体分析确定了“对I型干扰素（IFN）的反应”与24个I型IFN相关基因。RT-qPCR证实，使用24个基因计算的得分与使用OAS3，MX1和IFIT3（I型IFN得分）（rho与I型IFN得分0.981）所计算的得分之间存在很强的相关性；I型IFN评分在接受ABA治疗后显着降低（p <0.05），而未发生反应的患者则没有。接受者对I型IFN评分的工作特征曲线分析表明，对回应者的敏感性，特异性和AUC（95％置信区间）分别为0.82、1.00，和0.92（0.82-1.00）。此外，RT-qPCR证实应答者中BATF2，LAMP3，CD83，CLEC4A，IDO1，IRF7，STAT1，STAT2和TNFSF10的表达水平较高，它们都是与树突状细胞相关的基因或与I型IFN相关的基因，具有显着性生物学意义。结论I型IFN评分和这9个基因的表达水平可能是与RA患者对ABA的临床反应相关的新型生物标志物。