Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168, Rome, Italy.
Global Health Research Institute, Istituto di Igiene, Università Cattolica del Sacro Cuore, Rome, Italy.
Eur J Pediatr. 2023 May;182(5):2155-2167. doi: 10.1007/s00431-023-04844-1. Epub 2023 Feb 27.
Commercially available Interferon-γ release assays (IGRAs), including the last-generation QuantiFERON TB-Plus (QFT-Plus), are effective in aiding the diagnosis of tuberculosis (TB) infection but cannot distinguish latent TB subjects from active TB patients. The aim of this study was to prospectively evaluate the performance of an HBHA-based IGRA, combined with commercially available IGRAs, to assess their usefulness as a prognostic biomarkers and aid in the monitoring of TB treatment in children. Following clinical, microbiological, and radiological assessment, children younger than 18 years of age classified as either LTBI or active TB were tested at baseline and during treatment by the QuantiFERON TB-Plus (QFT) assay and an aliquot of whole-blood was stimulated with HBHA. Among the 655 children evaluated, 559 (85.3%) were classified as "Non TB", 44 patients (6.7%) with active TB, and 52 (7.9%) with LTBI. The median HBHA-IGRA IFN-gamma responses were able to discriminate active TB from LTBI (0.13 IU/ml vs 1.995, (p < 0,0001), those with asymptomatic TB from those with symptomatic TB (1.01 IU/ml vs 0.115 IU/ml, p 0.017), or more severe TB (p 0.022), and significantly raised during successful TB treatment (p < 0.0001). Conversely, CD4 + and CD8 + responses were similar in all groups of patients, although active TB patients had higher CD4 + responses and LTBI higher CD8 + responses. Conclusion: HBHA-based IGRA, combined with CD4 + and CD8 + responses assessed by commercially available IGRAs, is a useful support in the characterization of the TB spectrum in children and monitoring of TB-therapy. What is Known: • Current immune diagnostics are not able to discriminate active and latent Ttuberculosis, including the recently approved QFT-PLUS.. • New immunological assays with prognostic value are highly needed. What is New: • HBHA-based IGRA, combined with CD4+ and CD8+ responses assessed by commercially available IGRAs, is a useful support for the differentiation of active and latent TB in children.. • HBHA-based IGRA, combined with CD4+ and CD8+ responses assessed by commercially available IGRAs, is a useful support in the monitoring of TBtherapy in children..
市售的干扰素-γ释放试验（IGRAs），包括最新一代的 QuantiFERON TB-Plus（QFT-Plus），可有效辅助结核病（TB）感染的诊断，但无法区分潜伏性 TB 患者和活动性 TB 患者。本研究旨在前瞻性评估基于 HBHA 的 IGRAs 的性能，结合市售的 IGRAs，评估其作为预后生物标志物的有用性，并辅助儿童 TB 治疗的监测。在临床、微生物学和影像学评估后，将年龄小于 18 岁的 LTBI 或活动性 TB 患者分为两组，在基线和治疗期间分别使用 QuantiFERON TB-Plus（QFT）检测和全血标本用 HBHA 刺激。在评估的 655 名儿童中，559 名（85.3%）被归类为“非 TB”，44 名（6.7%）为活动性 TB，52 名（7.9%）为 LTBI。HBHA-IGRA IFN-γ 反应的中位数能够区分活动性 TB 和 LTBI（0.13IU/ml 与 1.995，（p<0.0001），无症状 TB 与有症状 TB（1.01IU/ml 与 0.115IU/ml，p0.017），或更严重的 TB（p0.022），并且在成功治疗 TB 期间显著升高（p<0.0001）。相反，所有患者组的 CD4+和 CD8+反应相似，尽管活动性 TB 患者的 CD4+反应更高，LTBI 患者的 CD8+反应更高。结论：基于 HBHA 的 IGRAs 与通过市售 IGRAs 评估的 CD4+和 CD8+反应相结合，是儿童 TB 谱特征和 TB 治疗监测的有用支持。已知：• 当前的免疫诊断无法区分活动性和潜伏性 TB，包括最近批准的 QFT-PLUS。• 迫切需要具有预后价值的新免疫测定法。新发现：• 基于 HBHA 的 IGRAs 与通过市售 IGRAs 评估的 CD4+和 CD8+反应相结合，是儿童中区分活动性和潜伏性 TB 的有用支持。• 基于 HBHA 的 IGRAs 与通过市售 IGRAs 评估的 CD4+和 CD8+反应相结合，是儿童 TB 治疗监测的有用支持。
