抗结核治疗后肺部和肺外结核的炎症蛋白和脂质介质谱仍存在变化：一项前瞻性队列研究。
Changes in inflammatory protein and lipid mediator profiles persist after antitubercular treatment of pulmonary and extrapulmonary tuberculosis: A prospective cohort study.
机构信息
Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil; Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Fundação José Silveira, Salvador 40210-320, Brazil; Curso de Medicina, Faculdade de Tecnologia e Ciências (FTC), Salvador 40290-150, Brazil.
Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Fundação José Silveira, Salvador 40210-320, Brazil.
出版信息
Cytokine. 2019 Nov;123:154759. doi: 10.1016/j.cyto.2019.154759. Epub 2019 Jun 18.
BACKGROUND
The identification of meaningful biomarkers of tuberculosis (TB) has potential to improve diagnosis, disease staging and prediction of treatment outcomes. It has been shown that active pulmonary TB (PTB) is associated with qualitative and quantitative changes in systemic immune profile, suggesting a chronic inflammatory imbalance. Here we characterized the profile of PTB and extrapulmonary TB (EPTB) in a prospective cohort study.
METHODS
We measured a panel of 27 inflammatory cytokines, soluble receptors, and lipid mediators in peripheral blood from patients with PTB or EPTB from a prospective clinical study in China. Multidimensional analyses were performed to describe associations between plasma levels of biomarkers and different TB disease presentation profiles.
RESULTS
Mycobacterium tuberculosis infection induced changes in both the expression and correlation profiles of plasma mediators of inflammation in patients with PTB compared to those with EPTB. Increases in mycobacterial loads in sputum smears were associated with rises in concentrations of several molecules involved in TB pathogenesis, such as IL-1β, IFN-α, IL-10 and PGF2α. Moreover, PTB patients presenting with severe disease exhibited a distinct inflammatory profile hallmarked by heightened levels of TNF-α, IL-1β, IL17, IL-18 and IL-27. Interestingly, while antitubercular treatment (ATT) resulted in early changes of plasma concentrations of markers in PTB, changes were delayed in EPTB patients. Exploratory analyses of the molecular degree of perturbation (MDP) of the inflammatory mediators before and during ATT suggested the occurrence of infection and/or treatment-induced long lasting "inflammatory imprinting" of biomarker profiles in TB. At 24 weeks post ATT commencement, markers underlying the observed increases in MDP scores were IL-27 in PTB and IL-1β in EPTB patients.
CONCLUSION
Our findings describe systemic and durable changes in the concentrations of inflammatory cytokines and lipid mediators in both PTB and EPTB and emphasize the role of M. tuberculosis bacterial burden and site of disease in modulating patient immune biomarkers.
背景
鉴定有意义的结核病（TB）生物标志物有可能改善诊断、疾病分期和预测治疗结果。已经表明，活动性肺结核（PTB）与全身免疫谱的定性和定量变化有关，表明存在慢性炎症失衡。在此，我们在一项前瞻性队列研究中对 PTB 和肺外结核（EPTB）的患者特征进行了描述。
方法
我们在中国的一项前瞻性临床研究中测量了 PTB 或 EPTB 患者外周血中 27 种炎症细胞因子、可溶性受体和脂质介质的谱。进行多维分析以描述生物标志物与不同 TB 疾病表现谱之间的关联。
结果
与 EPTB 相比，结核分枝杆菌感染引起 PTB 患者的炎症介质的表达和相关性谱发生变化。痰涂片的分枝杆菌负荷增加与参与结核病发病机制的几种分子（如 IL-1β、IFN-α、IL-10 和 PGF2α）的浓度升高有关。此外，患有严重疾病的 PTB 患者表现出独特的炎症谱，其特点是 TNF-α、IL-1β、IL17、IL-18 和 IL-27 的水平升高。有趣的是，虽然抗结核治疗（ATT）导致 PTB 患者的血浆标志物浓度早期发生变化，但 EPTB 患者的变化延迟。在 ATT 前后对炎症介质的分子扰动程度（MDP）进行探索性分析表明，在 TB 中，感染和/或治疗诱导的生物标志物谱的持久“炎症印记”发生。在 ATT 开始后 24 周时，导致观察到的 MDP 评分增加的标志物是 PTB 中的 IL-27 和 EPTB 中的 IL-1β。
结论
我们的研究结果描述了 PTB 和 EPTB 中炎症细胞因子和脂质介质浓度的系统性和持久变化，并强调了 M. tuberculosis 细菌负荷和疾病部位在调节患者免疫生物标志物中的作用。
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