The effects of infliximab therapy on the serum proteome of rheumatoid arthritis patients.
The effects of infliximab therapy on the serum proteome of rheumatoid arthritis patients.
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DOI：
10.1186/ar2637
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发表时间：
2009
影响因子：
4.9
通讯作者：
El-Gabalawy HS
中科院分区：
文献类型：
--
作者：
Dwivedi RC;Dhindsa N;Krokhin OV;Cortens J;Wilkins JA;El-Gabalawy HS
尽管英夫利昔单抗治疗类风湿性关节炎的临床效果已被广泛记载，但这种干预的生物学效应仍未得到明确。我们试图通过基于质谱的方法研究英夫利昔单抗治疗对类风湿关节炎患者血清蛋白质组的影响。使用标准临床方案，在英夫利昔单抗治疗12周之前和之后获得10例类风湿关节炎患者的血清。用iTRAQ（相对和绝对蛋白质定量等压标记）技术标记12种最高丰度的蛋白质，并通过质谱分析确定与治疗相关的蛋白质组学变化。每位患者平均鉴定出373种不同的蛋白质，置信度大于95%。在表现出最强劲临床反应的3例患者中，治疗后观察到39种蛋白质的血清水平变化超过20%。这些蛋白大部分受肿瘤坏死因子-α (TNF-α)和核因子- κ b直接或间接调控，急性期蛋白均下调。许多蛋白，包括SERPIN家族成员和S100A8，无论临床反应如何，都被下调。目前的研究表明，英夫利昔单抗的强劲临床反应与TNF-α调节的血清蛋白谱的下调有关，并为确定体内治疗的更广泛生物学效应提供了可能的基础。
Although the clinical effects of infliximab therapy in rheumatoid arthritis have been documented extensively, the biological effects of this intervention continue to be defined. We sought to examine the impact of infliximab therapy on the serum proteome of rheumatoid arthritis patients by means of a mass spectrometry-based approach. Sera from 10 patients with rheumatoid arthritis were obtained prior to and following 12 weeks of infliximab therapy using a standard clinical protocol. The sera were immunodepleted of the 12 highest abundance proteins, labeled by the iTRAQ (isobaric tagging for relative and absolute protein quantification) technique, and analyzed by mass spectrometry to identify proteomic changes associated with treatment. An average of 373 distinct proteins were identified per patient with greater than 95% confidence. In the 3 patients demonstrating the most robust clinical responses, changes of greater than 20% in the serum levels were observed in 39 proteins following treatment. The majority of these proteins were regulated directly or indirectly by tumour necrosis factor-alpha (TNF-α) and nuclear factor-kappa-B, with acute-phase proteins being uniformly down-regulated. A number of proteins, including members of the SERPIN family and S100A8, were down-regulated irrespective of clinical response. The present study demonstrates that a robust clinical response to infliximab is associated with the down-regulation of a spectrum of serum proteins regulated by TNF-α, and provides a possible basis for defining the broader biological effects of the treatment in vivo.
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影响因子：
--
作者：
de Seny, D;Fillet, M;Merville, MP
通讯作者：
Merville, MP
影响因子：
12.8
作者：
Ingegnoli, Francesca;Fantini, Flavio;Cugno, Massimo
通讯作者：
Cugno, Massimo
影响因子：
7.4
作者：
Spicer, Vic;Yamchuk, Andriy;Krokhin, Oleg V.
通讯作者：
Krokhin, Oleg V.
影响因子：
158.5
作者：
HEIJBOER, H;BRANDJES, DPM;TENCATE, JW
通讯作者：
TENCATE, JW
影响因子：
7.4
作者：
Gilar, M;Olivova, P;Gebler, JC
通讯作者：
Gebler, JC