Sudbury Eva L, Otero Larissa, Tebruegge Marc, Messina Nicole L, Seas Carlos, Montes Martin, Rìos Julia, Germano Susie, Gardiner Kaya, Clifford Vanessa, Gotuzzo Eduardo, Curtis Nigel
Department of Paediatrics, The University of Melbourne, Parkville, Australia.
Murdoch Children's Research Institute, Parkville, Australia.
J Clin Tuberc Other Mycobact Dis. 2019 Apr 25;16:100102. doi: 10.1016/j.jctube.2019.100102. eCollection 2019 Aug.
The tuberculin skin test and interferon-gamma release assays have limitations in diagnosing tuberculosis (TB), particularly in children. This study investigated the performance of candidate -specific cytokine biomarkers for TB in children in a TB-endemic setting. A total of 237 children with a household contact with smear-positive pulmonary TB were recruited. Importantly, a group of children with illnesses other than TB (sick controls) was included to assess specificity. Median IFN-ɣ, IL-1ra, IL-2, IL-13, IP-10, MIP-1β and TNF-α responses were significantly higher in children with active TB and latent TB infection (LTBI) than in both healthy and sick control children. Three of these cytokines - IL-2, IL-13 and IP-10 - showed better performance characteristics than IFN-ɣ, with IL-2 achieving positive and negative predictive values of 97.7% and 90.7%, respectively. Furthermore, IL-1ra and TNF-α responses differed significantly between active TB and LTBI cases, suggesting that they may be stage-specific biomarkers. Our data indicate that incorporating these biomarkers into future blood-based TB assays could result in substantial performance gains.
结核菌素皮肤试验和γ-干扰素释放试验在诊断结核病（TB）方面存在局限性，尤其是在儿童中。本研究调查了在结核病流行地区儿童中结核特异性细胞因子生物标志物的性能。共招募了237名与涂片阳性肺结核患者有家庭接触的儿童。重要的是，纳入了一组患有非结核疾病的儿童（患病对照）以评估特异性。活动性结核病和潜伏性结核感染（LTBI）儿童的IFN-γ、IL-1ra、IL-2、IL-13、IP-10、MIP-1β和TNF-α反应中位数显著高于健康和患病对照儿童。其中三种细胞因子——IL-2、IL-13和IP-10——表现出比IFN-γ更好的性能特征，IL-2的阳性和阴性预测值分别达到97.7%和90.7%。此外，活动性结核病和LTBI病例之间的IL-1ra和TNF-α反应存在显著差异，表明它们可能是阶段特异性生物标志物。我们的数据表明，将这些生物标志物纳入未来基于血液的结核病检测中可能会显著提高检测性能。
