Bacterial Diseases Programme, Medical Research Council Laboratories, Banjul, The Gambia.
PLoS One. 2010 Aug 24;5(8):e12365. doi: 10.1371/journal.pone.0012365.
Mycobacterium tuberculosis (MTb) infects approximately 2 billion people world-wide resulting in almost 2 million deaths per year. Determining biomarkers that distinguish different stages of tuberculosis (TB) infection and disease will provide tools for more effective diagnosis and ultimately aid in the development of new vaccine candidates. The current diagnostic kits utilising production of IFN-gamma in response to TB antigens can detect MTb infection but are unable to distinguish between infection and disease. The aim of this study was to assess if the use of a longer term assay and the analysis of multiple cytokines would enhance diagnosis of active TB in a TB-endemic population.
We compared production of multiple cytokines (TNF-alpha, IFN-gamma, IL-10, IL-12(p40), IL-13, IL-17 and IL-18) following long-term (7 days) stimulation of whole-blood with TB antigens (ESAT-6/CFP-10 (EC), PPD or TB10.4) from TB cases (n = 36) and their Mycobacterium-infected (TST+; n = 20) or uninfected (TST-; n = 19) household contacts (HHC).
We found that TNF-alpha production following EC stimulation and TNF-alpha and IL-12(p40) following TB10.4 stimulation were significantly higher from TB cases compared to TST+ HHC, while production of IFN-gamma and IL-13 were significantly higher from TST+ compared to TST- HHC following PPD or EC stimulation. Combined analysis of TNF-alpha, IL-12(p40) and IL-17 following TB10.4 stimulation resulted in 85% correct classification into TB cases or TST+ HHC. 74% correct classification into TST+ or TST- HHC was achieved with IFN-gamma alone following TB10.4 stimulation (69% following EC) and little enhancement was seen with additional cytokines. We also saw a tendency for TB cases infected with M. africanum to have increased TNF-alpha and IL-10 production compared to those infected with M. tuberculosis. Our results provide further insight into the pathogenesis of tuberculosis and may enhance the specificity of the currently available diagnostic tests, particularly for diagnosis of active TB.
结核分枝杆菌（MTb）感染全球约 20 亿人，导致每年近 200 万人死亡。确定区分结核病（TB）感染和疾病不同阶段的生物标志物，将为更有效的诊断提供工具，并最终有助于开发新的疫苗候选物。目前利用 TB 抗原刺激产生 IFN-γ的诊断试剂盒可检测 MTb 感染，但无法区分感染和疾病。本研究旨在评估使用长期检测和分析多种细胞因子是否能提高 TB 流行地区活动性 TB 的诊断能力。
我们比较了 36 例 TB 病例（TB 组）及其结核分枝杆菌感染（TST+；n=20）或未感染（TST-；n=19）的家庭接触者（HHC）在 TB 抗原（ESAT-6/CFP-10[EC]、PPD 或 TB10.4）刺激下长期（7 天）培养后产生的多种细胞因子（TNF-α、IFN-γ、IL-10、IL-12（p40）、IL-13、IL-17 和 IL-18）的情况。
我们发现与 TST+ HHC 相比，EC 刺激后 TNF-α的产生以及 TB10.4 刺激后 TNF-α和 IL-12（p40）的产生在 TB 组中明显更高，而 PPD 或 EC 刺激后，TST+ HHC 中 IFN-γ和 IL-13 的产生明显更高。TB10.4 刺激后联合分析 TNF-α、IL-12（p40）和 IL-17 的结果可使 85%的 TB 病例或 TST+ HHC 得到正确分类。仅用 TB10.4 刺激后 IFN-γ可使 74%的 TST+或 TST- HHC 得到正确分类（用 EC 刺激后为 69%），而添加其他细胞因子的效果则较小。我们还发现，感染非洲分枝杆菌的 TB 病例与感染结核分枝杆菌的病例相比，TNF-α和 IL-10 的产生量有增加的趋势。我们的研究结果进一步深入了解了结核病的发病机制，并可能提高目前诊断检测的特异性，特别是对活动性 TB 的诊断。
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