Druszczynska Magdalena, Seweryn Michal, Wawrocki Sebastian, Kowalewska-Pietrzak Magdalena, Pankowska Anna, Rudnicka Wieslawa
Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Im-munology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland.
Biobank Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland.
Pathogens. 2021 Apr 24;10(5):517. doi: 10.3390/pathogens10050517.
None of the currently used diagnostic tools are efficient enough in diagnosing Mycobacterium tuberculosis (M.tb) infection in children. The study was aimed to identify cytokine biosignatures characterizing active and latent tuberculosis (TB) in children. Using a multiplex bead-based technology, we analyzed the levels of 53 Th17-related cytokines and inflammatory mediators in sera from 216 BCG-vaccinated children diagnosed with active TB (TB) or latent TB (LTBI) as well as uninfected controls (HC). Children with active TB, compared to HC children, showed reduced serum levels of IL-17A, MMP-2, OPN, PTX-3, and markedly elevated concentrations of APRIL/TNFSF13. IL-21, sCD40L, MMP-2, and IL-8 were significantly differentially expressed in the comparisons between groups: (1) HC versus TB and LTBI (jointly), and (2) TB versus LTBI. The panel consisting of APRIL/TNFSF13, sCD30/TNFRSF8, IFN-α2, IFN-γ, IL-2, sIL-6Rα, IL-8, IL-11, IL-29/IFN-λ1, LIGHT/TNFSF14, MMP-1, MMP-2, MMP-3, osteocalcin, osteopontin, TSLP, and TWEAK/TNFSF12 possessed a discriminatory potential for the differentiation between TB and LTBI children. Serum-based host biosignatures carry the potential to aid the diagnosis of childhood M.tb infections. The proposed panels of markers allow distinguishing not only children infected with M.tb from uninfected individuals but also children with active TB from those with latent TB.
目前使用的诊断工具在诊断儿童结核分枝杆菌（M.tb）感染方面均不够高效。本研究旨在确定表征儿童活动性和潜伏性结核病（TB）的细胞因子生物标志物。我们采用基于多重微珠的技术，分析了216名接种卡介苗、被诊断为活动性结核病（TB）或潜伏性结核感染（LTBI）的儿童以及未感染对照（HC）血清中53种与Th17相关的细胞因子和炎症介质的水平。与HC儿童相比，活动性TB儿童血清中IL-17A、MMP-2、骨桥蛋白（OPN）、PTX-3水平降低，而增殖诱导配体/肿瘤坏死因子超家族成员13（APRIL/TNFSF13）浓度显著升高。在以下两组比较中，IL-21、可溶性CD40配体（sCD40L）、MMP-2和IL-8存在显著差异表达：（1）HC与TB和LTBI（合并），以及（2）TB与LTBI。由APRIL/TNFSF13、可溶性CD30/肿瘤坏死因子受体超家族成员8（sCD30/TNFRSF8）、干扰素α2（IFN-α2）、干扰素γ（IFN-γ）、白细胞介素2（IL-2）、可溶性白细胞介素6受体α（sIL-6Rα）、IL-8、IL-11、白细胞介素29/干扰素λ1（IL-29/IFN-λ1）、淋巴毒素样诱导物/肿瘤坏死因子超家族成员14（LIGHT/TNFSF14）、基质金属蛋白酶1（MMP-1）、MMP-2、MMP-3、骨钙素、骨桥蛋白、胸腺基质淋巴细胞生成素（TSLP）和肿瘤坏死因子相关弱凋亡诱导因子/肿瘤坏死因子超家族成员12（TWEAK/TNFSF12）组成的检测组具有区分TB和LTBI儿童的潜力。基于血清的宿主生物标志物具有辅助诊断儿童M.tb感染的潜力。所提出的标志物组不仅可以区分感染M.tb的儿童与未感染个体，还可以区分活动性TB儿童与潜伏性TB儿童。
