Chegou Novel N, Essone Paulin N, Loxton Andre G, Stanley Kim, Black Gillian F, van der Spuy Gian D, van Helden Paul D, Franken Kees L, Parida Shreemanta K, Klein Michel R, Kaufmann Stefan H E, Ottenhoff Tom H M, Walzl Gerhard
Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.
PLoS One. 2012;7(6):e38501. doi: 10.1371/journal.pone.0038501. Epub 2012 Jun 5.
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.
最近基于干扰素γ（IFN-γ）的研究已鉴定出新型结核分枝杆菌（M.tb）感染阶段依赖性抗原作为诊断候选物。在本研究中，评估了在用M.tb感染阶段依赖性抗原刺激后的全血培养上清液中除IFN-γ之外的11种宿主标志物的水平，用于结核病的诊断。
在一项病例对照研究中评估了五种M.tb感染阶段依赖性抗原，包括三种DosR调节子编码蛋白（Rv2032、Rv0081、Rv1737c）和两种复苏促进因子（Rv0867c和Rv2389c），该研究纳入了从南非开普敦高结核病发病率地区招募的15例肺结核患者和15名家庭接触者。经过7天的全血培养后，收集上清液并使用Luminex平台评估宿主标志物的水平。鉴定出多种具有潜在诊断潜力的抗原特异性宿主标志物。Rv0081特异性的IL-12（p40）、IP-10、IL-10和TNF-α水平是最有前景的诊断候选物，每种在诊断结核病时的准确率均为100%，受试者工作特征曲线下面积的95%置信区间为（1.0至1.0）。
在用M.tb感染阶段依赖性抗原刺激后的全血培养上清液中，除IFN-γ之外的多种细胞因子有望作为活动性结核病的诊断标志物。这些初步发现应在采用短期培养测定的精心设计的诊断研究中得到验证。
