Laboratory of Immunology, Robert Debré Hospital, AP-HP-Faculty of Medicine, Paris 7 Denis Diderot University, Paris, France.
Pediatr Res. 2012 Oct;72(4):370-4. doi: 10.1038/pr.2012.89. Epub 2012 Jul 13.
Distinguishing latent tuberculosis (LTB) from tuberculosis (TB) disease may be challenging in children. Here, we analyzed cytokine profiles that can distinguish the two infection stages in a nonendemic country (France).
Immunocompetent children with LTB (n = 6) or TB disease (n = 8) (median age: 6.2 and 5.7 years, respectively) were analyzed. Four young uninfected children were included as controls. A Luminex assay evaluated cytokine responses to Mycobacterium tuberculosis antigens.
Poor interleukin-4 (IL-4) and IL-10 responses precluded analysis of these cytokines. Interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-2, and T-helper type 1 (Th1) cytokines and IL-5, IL-13, T-helper type 2 (Th2) cytokines were simultaneously induced by antigens in 14/14 infected but 0/4 uninfected children. Th1 cytokine levels were similar in LTB and TB disease: IFN-γ: 12,254 and 10,495 pg/ml; IL-2: 2,097 and 1,869 pg/ml; and TNF-α: 1,020 and 2,875 pg/ml, respectively. Th2 cytokine levels were similar and even higher in LTB than in TB disease: IL-5: 23 and 10 pg/ml; IL-13: 284 and 109 pg/ml, respectively. Positive correlation of cytokine levels, whether Th1 or Th2, was observed. Higher (P = 0.008) TNF-α/IL-2 ratios distinguished 6/8 active TB disease cases from 6/6 LTB cases.
TNF-α/IL-2 ratio may discriminate TB disease from LTB in immunocompetent children. Larger studies in TB endemic settings must verify these results.
在非流行地区（法国），区分潜伏性结核（LTBI）和结核病（TB）可能具有挑战性。在这里，我们分析了可区分两种感染阶段的细胞因子谱。
分析了 6 例 LTBI 患儿和 8 例 TB 患儿（中位年龄分别为 6.2 岁和 5.7 岁），还纳入了 4 名未感染的年轻儿童作为对照。使用 Luminex 检测评估了针对结核分枝杆菌抗原的细胞因子反应。
IL-4 和 IL-10 反应不佳，无法对此两种细胞因子进行分析。IFN-γ、TNF-α、IL-2、Th1 细胞因子和 IL-5、IL-13、Th2 细胞因子在 14/14 例感染但 0/4 例未感染的儿童中同时被抗原诱导。LTBI 和 TB 疾病中的 Th1 细胞因子水平相似：IFN-γ：12254 和 10495 pg/ml；IL-2：2097 和 1869 pg/ml；TNF-α：1020 和 2875 pg/ml。LTBI 中的 Th2 细胞因子水平相似，甚至更高：IL-5：23 和 10 pg/ml；IL-13：284 和 109 pg/ml。Th1 或 Th2 细胞因子水平均呈正相关。较高的 TNF-α/IL-2 比值（P=0.008）可将 6/8 例活动性 TB 疾病与 6/6 例 LTBI 病例区分开来。
TNF-α/IL-2 比值可区分免疫功能正常的儿童中的 TB 疾病和 LTBI。在结核病流行地区，必须进一步开展更大规模的研究来验证这些结果。
