Introduction: There is active interest in leveraging host immune responses as biomarkers of tuberculosis (TB) disease activity. We had previously evaluated an immunodiagnostic test called the antibody in lymphocyte supernatant (ALS) assay. Here, we aimed to evaluate a panel of inflammatory mediators and associate the responses with the ALS results to identify a biosignature to distinguish TB cases from controls.
Methodology: In this case–control study, adults with TB were compared to controls who were hospitalized for non-infectious conditions. Blood was collected at baseline and after 4 weeks of TB treatment (from TB cases only). Peripheral blood mononuclear cells were isolated and cultured without antigenic stimulation for 72 hours. Inflammatory mediators were measured using the Multiplex cytokine kit and compared between TB cases and controls; among TB cases, responses were compared over time. ALS and inflammatory mediator results were evaluated using generalized discriminant analysis to identify the optimal biosignature to predict TB.
Results: When comparing inflammatory mediators between groups, IL-1ra, IL-1β, and granulocyte macrophage-colony stimulating factor (GM-CSF) were lower in TB cases (P<0.002). Fibroblast growth factor-basic significantly increased from baseline to week-4 (P=0.002). Generalized discriminant analysis yielded a model with IL-2, tumor necrosis factor-alpha, vascular endothelial growth factor, and ALS, providing a sensitivity of 82.2% and specificity of 76.2%.
Conclusion: Our results suggest that IL-1ra, IL-1β, and GM-CSF might be used as diagnostic biomarkers to distinguish between TB cases and non-TB cases. We could not identify a group of mediators that outperformed the diagnostic accuracy of the ALS alone.

Keywords: cytokines, chemokines, biomarkers, TB, diagnostics


中文翻译：

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评估外周血单核细胞上清液中的细胞因子用于结核病的诊断。


简介：人们对利用宿主免疫反应作为结核病 (TB) 疾病活动的生物标志物产生了浓厚的兴趣。我们之前评估了一种称为淋巴细胞上清液抗体 (ALS) 测定的免疫诊断测试。在这里，我们的目的是评估一组炎症介质，并将反应与 ALS 结果关联起来，以确定区分结核病例和对照的生物特征。

方法：在这项病例对照研究中，将患有结核病的成人与因非感染性疾病住院的对照者进行比较。在基线时和结核病治疗 4 周后采集血液（仅从结核病例中采集）。分离外周血单个核细胞，无抗原刺激培养72小时。使用 Multiplex 细胞因子试剂盒测量炎症介质，并在结核病病例和对照之间进行比较；在结核病病例中，随着时间的推移，对反应进行了比较。使用广义判别分析评估 ALS 和炎症介质结果，以确定预测结核病的最佳生物特征。

结果：比较各组间炎症介质时，结核病例中IL-1ra、IL-1β和粒细胞巨噬细胞集落刺激因子（GM-CSF）较低（ P <0.002）。碱性成纤维细胞生长因子从基线到第 4 周显着增加（ P = 0.002）。广义判别分析产生了包含 IL-2、肿瘤坏死因子-α、血管内皮生长因子和 ALS 的模型，灵敏度为 82.2%，特异性为 76.2%。

结论：我们的结果表明，IL-1ra、IL-1β 和 GM-CSF 可用作诊断生物标志物来区分结核病例和非结核病例。我们无法确定一组介质的诊断准确性优于单独的 ALS。


关键词：细胞因子、趋化因子、生物标志物、结核病、诊断