Multiplex analysis of cytokines/chemokines as biomarkers that differentiate healthy contacts from tuberculosis patients in high endemic settings
Multiplex analysis of cytokines/chemokines as biomarkers that differentiate healthy contacts from tuberculosis patients in high endemic settings
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DOI：
10.1016/j.cyto.2012.12.031
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发表时间：
2013-03-01
期刊：
影响因子：
3.8
通讯作者：
Raja, Alamelu
中科院分区：
文献类型：
--
作者：
Anbarasu, D.;Raja, C. Ponnu;Raja, Alamelu
区分结核病潜伏感染（LTBI）与活动性疾病是控制结核病的关键因素之一。在结核病流行的印度人群中，我们发现10种结核分枝杆菌分泌的蛋白组分仅在结核病患者（HC）的健康接触者中诱导IFN-γ应答，而在结核病患者（TB）中不诱导IFN-γ应答。这些级分被称为"接触特异性级分"（"CS"级分），并发现可用于区分HC与TB。蛋白质组学分析显示，"CS"级分有16种不同的蛋白质，其中三种是新的T细胞抗原。使用这些"CS"级分作为刺激物，研究了早期IFN-γ、TNF-α和IL-4细胞因子应答。在本研究中，为了鉴定在HC和TB之间差异表达的其他有用的细胞因子生物标志物，使用多重细胞因子测定系统分析细胞因子/趋化因子对"CS"级分的响应。在我们的结核病流行人群中进行的这项初步调查首次显示了HC和TB之间差异表达的六种细胞因子（G-CSF，IL-6，IL-7，IL-8，IL-9和PDGF）和一种受体拮抗剂（IL-1Ra）。尤其是IL-6和PDGF是更有前景的生物标志物。IL-6测量确定10个HC中有7个为HC。PDGF的测量确定了10个TB中的8个TB。正在进行研究以进一步验证这些生物标志物用于区分LTBI与活动性结核病。(C)2013爱思唯尔有限公司保留所有权利。
Differentiation of latent tuberculosis infection (LTBI) from active disease is one of the crucial elements in the control of tuberculosis. Earlier in Indian population which is tuberculosis endemic, we identified that 10 Mycobacterium tuberculosis secreted protein fractions, induced IFN-gamma response only in healthy contacts of TB patients (HCs) and not in tuberculosis patients (TB). These fractions were termed as "Contact Specific Fractions" ("CS" fractions) and found useful for differentiating HC from TB. Proteomic analysis revealed that "CS" fractions have 16 different proteins, of which three were novel T cell antigens. Using these "CS" fractions as stimulants, earlier IFN-gamma, TNF-alpha and IL-4 cytokine responses were studied. In the present study, in order to identify the other useful cytokine biomarkers that were differentially expressed between HC and TB, Cytokine/chemokine response to "CS" fractions were analyzed using multiplex cytokine assay system. This preliminary investigation in our tuberculosis endemic population showed six cytokine (G-CSF, IL-6, IL-7, IL-8, IL-9, and PDGF) and one receptor antagonist (IL-1Ra) that were differentially expressed between HC and TB, for the first time. Especially IL-6 and PDGF were more promising biomarkers. IL-6 measurement identified seven as HC out of 10 HC analyzed. The measurement of PDGF identified eight as TB out of 10 TB tested. Studies are underway to further validate these biomarkers for the differentiation of LTBI from active tuberculosis. (C) 2013 Elsevier Ltd. All rights reserved.