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Abstract：
UNASSIGNED: The diagnosis of tuberculosis (TB) disease and TB infection (TBI) remains a challenge, and there is a need for non-invasive and blood-based methods to differentiate TB from conditions mimicking TB (CMTB), TBI, and healthy controls (HC). We aimed to determine whether combination of cytokines and established biomarkers could discriminate between 1) TB and CMTB 2) TB and TBI 3) TBI and HC.
UNASSIGNED: We used hemoglobin, total white blood cell count, neutrophils, monocytes, C-reactive protein, and ten Meso Scale Discovery analyzed cytokines (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon (IFN)-ɣ, and tumor necrosis factor (TNF)-α) in TruCulture whole blood tubes stimulated by lipopolysaccharides (LPS), zymosan (ZYM), anti-CD3/28 (CD3), and unstimulated (Null) to develop three index tests able to differentiate TB from CMTB and TBI, and TBI from HC.
UNASSIGNED: In 52 persons with CMTB (n=9), TB (n=23), TBI (n=10), and HC (n=10), a combination of cytokines (LPS-IFN-ɣ, ZYM-IFN-ɣ, ZYM-TNF-α, ZYM-IL-1β, LPS-IL-4, and ZYM-IL-6) and neutrophil count could differentiate TB from CMTB with a sensitivity of 52.2% (95% CI: 30.9%-73.4%) and a specificity of 100 % (66.4%-100%). Null- IFN-ɣ, Null-IL-8, CD3-IL-6, CD3-IL-8, CD3-IL-13, and ZYM IL-1b discriminated TB from TBI with a sensitivity of 73.9% (56.5% - 91.3%) and a specificity of 100% (69.2-100). Cytokines and established biomarkers failed to differentiate TBI from HC with ≥ 98% specificity.
UNASSIGNED: Selected cytokines may serve as blood-based add-on tests to detect TB in a low-endemic setting, although these results need to be validated.
UNASSIGNED: We used hemoglobin, total white blood cell count, neutrophils, monocytes, C-reactive protein, and ten Meso Scale Discovery analyzed cytokines (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon (IFN)-ɣ, and tumor necrosis factor (TNF)-α) in TruCulture whole blood tubes stimulated by lipopolysaccharides (LPS), zymosan (ZYM), anti-CD3/28 (CD3), and unstimulated (Null) to develop three index tests able to differentiate TB from CMTB and TBI, and TBI from HC.
UNASSIGNED: In 52 persons with CMTB (n=9), TB (n=23), TBI (n=10), and HC (n=10), a combination of cytokines (LPS-IFN-ɣ, ZYM-IFN-ɣ, ZYM-TNF-α, ZYM-IL-1β, LPS-IL-4, and ZYM-IL-6) and neutrophil count could differentiate TB from CMTB with a sensitivity of 52.2% (95% CI: 30.9%-73.4%) and a specificity of 100 % (66.4%-100%). Null- IFN-ɣ, Null-IL-8, CD3-IL-6, CD3-IL-8, CD3-IL-13, and ZYM IL-1b discriminated TB from TBI with a sensitivity of 73.9% (56.5% - 91.3%) and a specificity of 100% (69.2-100). Cytokines and established biomarkers failed to differentiate TBI from HC with ≥ 98% specificity.
UNASSIGNED: Selected cytokines may serve as blood-based add-on tests to detect TB in a low-endemic setting, although these results need to be validated.
摘要：
■结核病（TB）和结核感染（TBI）的诊断仍然是一个挑战，并且需要非侵入性和基于血液的方法来区分TB与模拟TB（CMTB）的条件，TBI,和健康对照（HC）。我们旨在确定细胞因子和已建立的生物标志物的组合是否可以区分1）TB和CMTB2）TB和TBI3）TBI和HC。
■我们使用了血红蛋白，白细胞总数,中性粒细胞，单核细胞,C反应蛋白,和十个中观尺度发现分析了细胞因子(白细胞介素(IL)-1β，IL-2、IL-4、IL-6、IL-8、IL-10、IL-12p70、IL-13、干扰素(IFN)和肿瘤坏死因子（TNF）-α）在脂多糖（LPS）刺激的TruCulture全血试管中，酵母聚糖(ZYM)，抗CD3/28（CD3），和无刺激（空）开发三个指标测试，能够区分结核病从CMTB和TBI，和HC的TBI。
■在52名CMTB患者中（n=9），TB（n=23），TBI（n=10），和HC(n=10)，细胞因子的组合(LPS-IFN-,ZYM-IFN-，ZYM-TNF-α,ZYM-IL-1β，LPS-IL-4和ZYM-IL-6）和中性粒细胞计数可将TB与CMTB区分开，敏感性为52.2％（95％CI：30.9％-73.4％），特异性为100％（66.4％-100％）。Null-IFN-，空-IL-8、CD3-IL-6、CD3-IL-8、CD3-IL-13和ZYMIL-1b将TB与TBI区分开来,其灵敏度为73.9%(56.5%-91.3%),特异性为100%(69.2-100)。细胞因子和已建立的生物标志物未能区分TBI和HC，特异性≥98%。
■选定的细胞因子可以作为血液的附加测试，以检测低流行环境中的结核病，尽管这些结果需要验证。
■我们使用了血红蛋白，白细胞总数,中性粒细胞，单核细胞,C反应蛋白,和十个中观尺度发现分析了细胞因子(白细胞介素(IL)-1β，IL-2、IL-4、IL-6、IL-8、IL-10、IL-12p70、IL-13、干扰素(IFN)和肿瘤坏死因子（TNF）-α）在脂多糖（LPS）刺激的TruCulture全血试管中，酵母聚糖(ZYM)，抗CD3/28（CD3），和无刺激（空）开发三个指标测试，能够区分结核病从CMTB和TBI，和HC的TBI。
■在52名CMTB患者中（n=9），TB（n=23），TBI（n=10），和HC(n=10)，细胞因子的组合(LPS-IFN-,ZYM-IFN-
■选定的细胞因子可以作为血液的附加测试，以检测低流行环境中的结核病，尽管这些结果需要验证。
