ICMR-National Institute for Research in Tuberculosis, Chennai, India.
Institute of Child Health and Hospital for Children, Chennai, India.
BMC Infect Dis. 2021 Oct 11;21(1):1055. doi: 10.1186/s12879-021-06749-6.
Diagnosing tuberculosis (TB) in children is challenging due to paucibacillary disease, and lack of ability for microbiologic confirmation. Hence, we measured the plasma chemokines as biomarkers for diagnosis of pediatric tuberculosis.
We conducted a prospective case control study using children with confirmed, unconfirmed and unlikely TB. Multiplex assay was performed to examine the plasma CC and CXC levels of chemokines.
Baseline levels of CCL1, CCL3, CXCL1, CXCL2 and CXCL10 were significantly higher in active TB (confirmed TB and unconfirmed TB) in comparison to unlikely TB children. Receiver operating characteristics curve analysis revealed that CCL1, CXCL1 and CXCL10 could act as biomarkers distinguishing confirmed or unconfirmed TB from unlikely TB with the sensitivity and specificity of more than 80%. In addition, combiROC exhibited more than 90% sensitivity and specificity in distinguishing confirmed and unconfirmed TB from unlikely TB. Finally, classification and regression tree models also offered more than 90% sensitivity and specificity for CCL1 with a cutoff value of 28 pg/ml, which clearly classify active TB from unlikely TB. The levels of CCL1, CXCL1, CXCL2 and CXCL10 exhibited a significant reduction following anti-TB treatment.
Thus, a baseline chemokine signature of CCL1/CXCL1/CXCL10 could serve as an accurate biomarker for the diagnosis of pediatric tuberculosis.
由于疾病菌载量低和缺乏微生物学确认能力,儿童结核病的诊断具有挑战性。因此,我们测量了血浆趋化因子作为诊断儿童结核病的生物标志物。
我们进行了一项前瞻性病例对照研究,使用确诊、未确诊和不太可能患有结核病的儿童。采用多重分析方法检测趋化因子的血浆 CC 和 CXC 水平。
与不太可能患有结核病的儿童相比,活动性结核病(确诊结核病和未确诊结核病)的基线 CCL1、CCL3、CXCL1、CXCL2 和 CXCL10 水平明显更高。受试者工作特征曲线分析显示,CCL1、CXCL1 和 CXCL10 可以作为生物标志物,将确诊或未确诊的结核病与不太可能患有结核病区分开来,其敏感性和特异性均超过 80%。此外,combROC 在区分确诊和未确诊的结核病与不太可能患有结核病方面的敏感性和特异性均超过 90%。最后,分类和回归树模型也为 CCL1 提供了超过 90%的敏感性和特异性,其截断值为 28pg/ml,可以清楚地将活动性结核病与不太可能患有结核病区分开来。CCL1、CXCL1、CXCL2 和 CXCL10 的水平在抗结核治疗后显著降低。
因此,CCL1/CXCL1/CXCL10 的基线趋化因子特征可以作为儿童结核病诊断的准确生物标志物。