Analysis of complex biomarkers for human immune-mediated disorders based on cytokine responsiveness of peripheral blood cells.
Analysis of complex biomarkers for human immune-mediated disorders based on cytokine responsiveness of peripheral blood cells.
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DOI：
10.4049/jimmunol.0904180
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发表时间：
2010-06-15
期刊：
影响因子：
--
通讯作者：
Gabriel SE
中科院分区：
文献类型：
--
作者：
Davis JM 3rd;Knutson KL;Strausbauch MA;Crowson CS;Therneau TM;Wettstein PJ;Matteson EL;Gabriel SE
改进的生物标志物的出现有望加强类风湿性关节炎(RA)和其他免疫介导性疾病患者的临床护理。我们开发了一种创新的方法，使用多刺激物小组和多重免疫分析来广泛评估人PBMC的细胞因子反应性。这项研究的目的是通过确定细胞因子谱是否可以根据疾病阶段(早期和晚期)或严重程度区分RA患者来证明这一概念。10种细胞因子包括IL-12、CCL4、肿瘤坏死因子α、IL-4和IL-10在抗CD3/抗CD28刺激下的释放，CXCL8和IL-6在巨细胞病毒/EB病毒裂解物刺激下的释放，以及IL-17A、GM-CSF和CCL2在热休克蛋白60刺激下的反应，很容易区分早期RA组和对照组。这些数据被用来创建免疫反应评分，该评分在区分早期RA患者和对照组方面表现良好，也与晚期RA患者的疾病严重程度的几个标记物相关。相比之下，在血清中评估的相同的10种细胞因子谱在区分这两组方面的效果要差得多。因此，我们的方法为发展免疫学“特征”奠定了基础，这些特征可用于预测疾病进程和监测免疫介导性疾病患者的治疗结果。
The advent of improved biomarkers promises to enhance the clinical care for patients with rheumatoid arthritis (RA) and other immune-mediated disorders. We have developed an innovative approach to broadly assess the cytokine responsiveness of human PBMC using a multi-stimulant panel and multiplexed immunoassays. The objective of this study was to demonstrate this concept by determining whether cytokine profiles could discriminate RA patients according to disease stage (early vs. late) or severity. A 10-cytokine profile, consisting of IL-12, CCL4, TNFα, IL-4, and IL-10 release in response to stimulation with anti-CD3/anti-CD28, CXCL8 and IL-6 in response to CMV/EBV lysate, and IL-17A, GM-CSF, and CCL2 in response to HSP60, easily discriminated the early RA group from controls. These data were used to create an immune response score, which performed well in distinguishing the early RA patients from controls and also correlated with several markers of disease severity among the patients with late RA. In contrast, the same 10-cytokine profile assessed in serum was far less effective in discriminating the groups. Thus, our approach lays the foundation for the development of immunologic ‘signatures’ that could be useful in predicting disease course and monitoring the outcomes of therapy among patients with immune-mediated diseases.
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影响因子：
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