Abstract：
OBJECTIVE: The objective of this study was to assess differentially expressed blood proteins between patients with active RA and patients in remission after MTX treatment, with the aim of identifying a biomarker of MTX resistance (MTXR).
METHODS: Two populations of RA patients treated with a stable dose of s.c. MTX for at least 3 months were constituted according to the DAS28: remission (DAS28 < 2.6; n = 24) and active disease (DAS28 > 3.2; n = 32). The two groups of RA patients were homogeneous regarding their epidemiological characteristics, except for the duration of treatment, which was longer in the remission group. After collection of a blood sample, plasma protein digestion was performed, followed by untargeted proteomics analysis. Then, a targeted analysis was performed to confirm the results of the untargeted approach.
RESULTS: Untargeted proteomics analysis revealed eight plasma proteins that were differentially expressed between the two groups of patients. Among them, triosephosphate isomerase (TPI-1) and glucose-6-phosphate isomerase (GPI), which are main actors in glycolysis, were found down-regulated in the active group. This result was confirmed for TPI-1 in the targeted proteomics analysis.
CONCLUSIONS: A first step was achieved in the search for biomarkers of MTXR, with the identification of two actors in glycolysis (TPI-1 and GPI). The next step will be to confirm these results in a larger cohort, including samples from treatment-naive patients, to assess the predictive potential of these protein markers.
METHODS: Two populations of RA patients treated with a stable dose of s.c. MTX for at least 3 months were constituted according to the DAS28: remission (DAS28 < 2.6; n = 24) and active disease (DAS28 > 3.2; n = 32). The two groups of RA patients were homogeneous regarding their epidemiological characteristics, except for the duration of treatment, which was longer in the remission group. After collection of a blood sample, plasma protein digestion was performed, followed by untargeted proteomics analysis. Then, a targeted analysis was performed to confirm the results of the untargeted approach.
RESULTS: Untargeted proteomics analysis revealed eight plasma proteins that were differentially expressed between the two groups of patients. Among them, triosephosphate isomerase (TPI-1) and glucose-6-phosphate isomerase (GPI), which are main actors in glycolysis, were found down-regulated in the active group. This result was confirmed for TPI-1 in the targeted proteomics analysis.
CONCLUSIONS: A first step was achieved in the search for biomarkers of MTXR, with the identification of two actors in glycolysis (TPI-1 and GPI). The next step will be to confirm these results in a larger cohort, including samples from treatment-naive patients, to assess the predictive potential of these protein markers.
摘要：
目的：评估活动性类风湿关节炎（RA）患者与甲氨蝶呤（MTX）治疗后缓解期患者的血蛋白差异表达，目的是鉴定甲氨蝶呤耐药（MTXR）的生物标志物。
方法：根据DAS28：缓解（DAS28<2.6；n=24）和活动性疾病（DAS28>3.2；n=32）组成两组接受稳定剂量的皮下MTX治疗至少3个月的RA患者。两组RA患者的流行病学特征是同质的，除了缓解组的治疗持续时间更长。采集血样后,进行血浆蛋白消化，随后进行非靶向蛋白质组学分析。然后，我们进行了针对性分析,以确认非靶向方法的结果.
结果：非靶向蛋白质组学分析显示，两组患者之间有8种血浆蛋白差异表达。其中,磷酸三糖异构酶（TPI-1）和葡萄糖-6-磷酸异构酶（GPI），它们是糖酵解的主要参与者，在活性组中发现下调。TPI-1在靶向蛋白质组学分析中证实了该结果。
结论：在寻找MTXR的生物标志物过程中实现了第一步，同时鉴定了两种糖酵解作用者（TPI-1和GPI）。下一步将是在更大的队列中确认这些结果，包括初治患者的样本，评估这些蛋白质标记的预测潜力。
方法：根据DAS28：缓解（DAS28<2.6；n=24）和活动性疾病（DAS28>3.2；n=32）组成两组接受稳定剂量的皮下MTX治疗至少3个月的RA患者。两组RA患者的流行病学特征是同质的，除了缓解组的治疗持续时间更长。采集血样后,进行血浆蛋白消化，随后进行非靶向蛋白质组学分析。然后，我们进行了针对性分析,以确认非靶向方法的结果.
结果：非靶向蛋白质组学分析显示，两组患者之间有8种血浆蛋白差异表达。其中,磷酸三糖异构酶（TPI-1）和葡萄糖-6-磷酸异构酶（GPI），它们是糖酵解的主要参与者，在活性组中发现下调。TPI-1在靶向蛋白质组学分析中证实了该结果。
结论：在寻找MTXR的生物标志物过程中实现了第一步，同时鉴定了两种糖酵解作用者（TPI-1和GPI）。下一步将是在更大的队列中确认这些结果，包括初治患者的样本，评估这些蛋白质标记的预测潜力。
