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细胞因子特征模式的应用:区分未使用过药物、接受过干扰素和那他珠单抗治疗的多发性硬化症患者。

The use of cytokine signature patterns: separating drug naïve, interferon and natalizumab-treated multiple sclerosis patients.

作者信息

O'Connell Kara E, Mok Tzehow, Sweeney Brian, Ryan Aisling M, Dev Kumlesh K

机构信息

Drug Development, School of Medicine, Trinity College Dublin , Ireland .

出版信息

Autoimmunity. 2014 Dec;47(8):505-11. doi: 10.3109/08916934.2014.930734. Epub 2014 Jun 30.

Abstract

Multiple sclerosis (MS) is an inflammatory illness characterized by demyelination and axonal neurodegeneration. Here, we used serum samples from MS patients to demonstrate if "cytokine signature" patterns can separate different patient groups better than using single cytokines. In this case, we used cytokine profiling to demonstrate if "cytokine signature" patterns can separate MS patients treated with interferon or natalizumab from drug naïve patients. Serum levels of eight individual cytokines (TNFα, IFNγ, S100B, IL-1β, IL-6, IL-8, IL-17 and IL-23) in MS patients treated with interferons (n = 11) and natalizumab (n = 14) were measured and, in general, showed reduced levels compared to drug naïve MS patients (n = 12). More evident changes were seen when analyzing "cytokine signatures" (i.e. summed value of all eight cytokines), which showed that patients treated with natalizumab and interferons showed significantly reduced cytokine signature levels than drug naïve MS patients. Moreover, patients treated with natalizumab were separated from drug naïve patients by almost 100% fidelity and that patients treated with natalizumab also had reduced levels of pro-inflammatory cytokines compared to patients treated with interferon. Overall, this study provides an example showing that the use of "cytokine signatures" may provide benefits over the analysis of single cytokines for the development of potential biomarkers.

摘要

多发性硬化症(MS)是一种以脱髓鞘和轴突神经变性为特征的炎症性疾病。在此,我们使用MS患者的血清样本,以证明“细胞因子特征”模式是否比使用单一细胞因子能更好地区分不同患者组。在本研究中,我们使用细胞因子谱分析来证明“细胞因子特征”模式能否将接受干扰素或那他珠单抗治疗的MS患者与未接受过治疗的患者区分开来。对接受干扰素治疗的11例MS患者和接受那他珠单抗治疗的14例MS患者的8种单个细胞因子(TNFα、IFNγ、S100B、IL-1β、IL-6、IL-8、IL-17和IL-23)的血清水平进行了检测,总体而言,与未接受过治疗的12例MS患者相比,其水平有所降低。在分析“细胞因子特征”(即所有8种细胞因子的总和值)时,发现了更明显的变化,结果显示接受那他珠单抗和干扰素治疗的患者的细胞因子特征水平显著低于未接受过治疗的MS患者。此外,接受那他珠单抗治疗的患者与未接受过治疗的患者的区分准确率几乎达到100%,并且与接受干扰素治疗的患者相比,接受那他珠单抗治疗的患者的促炎细胞因子水平也有所降低。总体而言,本研究提供了一个实例,表明对于潜在生物标志物的开发,使用“细胞因子特征”可能比分析单一细胞因子更具优势。

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