Potential of host markers produced by infection phase-dependent antigen-stimulated cells for the diagnosis of tuberculosis in a highly endemic area.

Potential of host markers produced by infection phase-dependent antigen-stimulated cells for the diagnosis of tuberculosis in a highly endemic area.
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DOI:
10.1371/journal.pone.0038501
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Walzl G
Walzl G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chegou NN;Essone PN;Loxton AG;Stanley K;Black GF;van der Spuy GD;van Helden PD;Franken KL;Parida SK;Klein MR;Kaufmann SH;Ottenhoff TH;Walzl G

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最近基于干扰素γ(IFN-γ)的研究已经鉴定了新的结核分枝杆菌(M.tb)感染阶段依赖性抗原作为诊断候选物。在这项研究中,在用结核分枝杆菌感染阶段依赖性抗原刺激后,在全血培养上清液中评价了除IFN-γ以外的11种宿主标志物的水平,用于诊断TB疾病。在一项病例对照研究中,对5种结核分枝杆菌感染阶段依赖性抗原进行了评价,这些抗原包括3种DosR-调节子编码的蛋白质(Rv 2032、Rv 0081、Rv 1737 c)和2种再吸促进因子(Rv 0867 c和Rv 2389 c),研究对象为从南非开普敦结核病高发区招募的15名肺结核患者和15名家庭接触者。7天全血培养后,收获上清液,并使用Luminex平台评价宿主标志物的水平。多种抗原特异性宿主标记物被鉴定为具有很好的诊断潜力。Rv 0081特异性水平的IL-12(p40)、IP-10、IL-10和TNF-α是最有希望的诊断候选物,每一个都以100%的准确度确定TB疾病,对于受试者操作特征图下的面积的95%置信区间(1.0至1.0)。在用结核分枝杆菌感染阶段依赖性抗原刺激后,全血培养上清液中除IFN-γ以外的多种细胞因子显示出作为活动性TB的诊断标志物的前景。这些初步发现应在设计良好的诊断研究中采用短期培养试验进行验证。
Recent interferon gamma (IFN-γ)-based studies have identified novel Mycobacterium tuberculosis (M.tb) infection phase-dependent antigens as diagnostic candidates. In this study, the levels of 11 host markers other than IFN-γ, were evaluated in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens, for the diagnosis of TB disease. Five M.tb infection phase-dependent antigens, comprising of three DosR-regulon-encoded proteins (Rv2032, Rv0081, Rv1737c), and two resucitation promoting factors (Rv0867c and Rv2389c), were evaluated in a case-control study with 15 pulmonary TB patients and 15 household contacts that were recruited from a high TB incidence setting in Cape Town, South Africa. After a 7-day whole blood culture, supernatants were harvested and the levels of the host markers evaluated using the Luminex platform. Multiple antigen-specific host markers were identified with promising diagnostic potential. Rv0081-specific levels of IL-12(p40), IP-10, IL-10 and TNF-α were the most promising diagnostic candidates, each ascertaining TB disease with an accuracy of 100%, 95% confidence interval for the area under the receiver operating characteristics plots, (1.0 to 1.0). Multiple cytokines other than IFN-γ in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens show promise as diagnostic markers for active TB. These preliminary findings should be verified in well-designed diagnostic studies employing short-term culture assays.
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发表时间: 2011-03
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