Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia; Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia; Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, Parkville, VIC, Australia; Academic Unit of Clinical and Experimental Medicine, Faculty of Medicine & Respiratory Biomedical Research Unit & Global Health Research Institute, University of Southampton, United Kingdom.
J Infect. 2017 Aug;75(2):132-145. doi: 10.1016/j.jinf.2017.04.011. Epub 2017 May 5.
A biomarker indicating successful tuberculosis (TB) therapy would assist in determining appropriate length of treatment. This study aimed to determine changes in mycobacteria-specific antigen-induced cytokine biomarkers in patients receiving therapy for latent or active TB, to identify biomarkers potentially correlating with treatment success.
A total of 33 adults with active TB and 36 with latent TB were followed longitudinally over therapy. Whole blood stimulation assays using mycobacteria-specific antigens (CFP-10, ESAT-6, PPD) were done on samples obtained at 0, 1, 3, 6 and 9 months. Cytokine responses (IFN-γ, IL-1ra, IL-2, IL-10, IL-13, IP-10, MIP-1β, and TNF-α) in supernatants were measured by Luminex xMAP immunoassay.
In active TB cases, median IL-1ra (with CFP-10 and with PPD stimulation), IP-10 (CFP-10, ESAT-6), MIP-1β (ESAT-6, PPD), and TNF-α (ESAT-6) responses declined significantly over the course of therapy. In latent TB cases, median IL-1ra (CFP-10, ESAT-6, PPD), IL-2 (CFP-10, ESAT-6), and IP-10 (CFP-10, ESAT-6) responses declined significantly.
Mycobacteria-specific cytokine responses change significantly over the course of therapy, and their kinetics in active TB differ from those observed in latent TB. In particular, mycobacteria-specific IL-1ra responses are potential correlates of successful therapy in both active and latent TB.
一种能指示结核病（TB）治疗成功的生物标志物，将有助于确定适当的治疗时长。本研究旨在确定潜伏性或活动性结核病患者接受治疗时，分枝杆菌特异性抗原诱导的细胞因子生物标志物的变化，以确定可能与治疗成功相关的生物标志物。
对 33 例活动性 TB 患者和 36 例潜伏性 TB 患者进行了纵向随访，在治疗过程中分别于 0、1、3、6 和 9 个月采集样本进行分枝杆菌特异性抗原（CFP-10、ESAT-6、PPD）的全血刺激检测。通过 Luminex xMAP 免疫分析测量上清液中细胞因子反应（IFN-γ、IL-1ra、IL-2、IL-10、IL-13、IP-10、MIP-1β 和 TNF-α）。
在活动性 TB 病例中，随着治疗的进行，IL-1ra（CFP-10 和 PPD 刺激）、IP-10（CFP-10、ESAT-6）、MIP-1β（ESAT-6、PPD）和 TNF-α（ESAT-6）的中位数反应显著下降。在潜伏性 TB 病例中，CFP-10、ESAT-6 和 PPD 刺激的 IL-1ra、CFP-10 和 ESAT-6 刺激的 IL-2 和 CFP-10 和 ESAT-6 刺激的 IP-10 的中位数反应显著下降。
分枝杆菌特异性细胞因子反应在治疗过程中发生显著变化，其在活动性 TB 中的动力学与潜伏性 TB 中的观察结果不同。特别是分枝杆菌特异性 IL-1ra 反应可能是活动性和潜伏性 TB 治疗成功的潜在相关因素。
