Laboratory of Immunology, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Diderot, Sorbonne Paris Cité, 75019 Paris, France.
Department of Pediatric Infectious Disease, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Diderot, Sorbonne Paris Cité, 75019 Paris, France.
J Infect. 2015 Aug;71(2):250-7. doi: 10.1016/j.jinf.2015.03.014. Epub 2015 May 1.
An increased rate of indeterminate quantiferon results (low IFN-γ release in the phytohemagglutinin-stimulated tube) has been reported in children with clinical signs compatible with tuberculosis but with the final diagnosis of infectious diseases different from tuberculosis. Here, we addressed the mechanisms involved and assessed potential alternative biomarkers to overcome indeterminate quantiferon results under these conditions.
Cytokine concentrations were measured in residual plasma from quantiferon assays performed in immunocompetent children (cases, median age: 3 years 9 months) with indeterminate results and community acquired pneumonia (n = 7) or meningoencephalitis (n = 1). Controls were age-matched immunocompetent children with determinate quantiferon results (infected with mycobacterium tuberculosis, n = 7 or not, n = 8).
Lower IFN-γ expression in phytohemagglutinin-stimulated cultures from cases was accompanied by lower Th1 (IL-2, TNF-α, IP-10) and Th2 (IL-5, IL-13), but similar IL-10 secretion capacities as the controls.
A state of hyporesponsiveness that resembles the concept of immunoparalysis in severe infection was observed in children with milder infections. Though IP-10, IL-2, IL-5 and IL-13 were confirmed as promising alternative biomarkers for discriminating controls with and without tuberculosis in this study, defective induction of these biomarkers by phytohemagglutinin in cases precluded their usefulness in overcoming quantiferon indeterminate results in the above-mentioned clinical conditions.
在具有结核病临床症状但最终诊断为非结核病感染性疾病的儿童中，已报道其定量干扰素结果（植物血凝素刺激管中低 IFN-γ 释放）的发生率增加。在此，我们探讨了相关机制，并评估了在这些情况下克服定量干扰素不确定结果的潜在替代生物标志物。
我们测量了免疫功能正常的儿童（病例组，中位年龄：3 岁 9 个月）中定量干扰素检测结果不确定的社区获得性肺炎（n=7）或脑膜炎（n=1）患者剩余血浆中的细胞因子浓度。对照组为年龄匹配的定量干扰素检测结果确定的免疫功能正常儿童（感染结核分枝杆菌，n=7 或未感染，n=8）。
病例组植物血凝素刺激培养物中的 IFN-γ 表达较低，同时 Th1（IL-2、TNF-α、IP-10）和 Th2（IL-5、IL-13）表达较低，但与对照组的 IL-10 分泌能力相似。
在感染较轻的儿童中观察到一种类似于严重感染中免疫麻痹概念的低反应状态。虽然 IP-10、IL-2、IL-5 和 IL-13 在本研究中被证实是区分有无结核病的有前途的替代生物标志物，但植物血凝素对病例中这些生物标志物的诱导缺陷排除了它们在上述临床情况下克服定量干扰素不确定结果的有用性。
