关键词: TB treatment cure TB treatment failure cytokines recurrence tuberculosis

Mesh : Humans Tuberculosis, Pulmonary / immunology blood diagnosis drug therapy Cytokines / blood Male Female Adult Middle Aged Biomarkers / blood Antigens, Bacterial / immunology Treatment Outcome Antitubercular Agents / therapeutic use Mycobacterium tuberculosis / immunology Aged

来  源:   DOI:10.3389/fimmu.2024.1392256   PDF(Pubmed)

Abstract:
UNASSIGNED: The assessment of tuberculosis (TB) treatment outcomes predominantly relies on sputum culture conversion status. To enhance treatment management, it is crucial to identify non-sputum-based biomarkers that can predict unfavorable outcomes. Cytokines are widely studied as diagnostic biomarkers for active TB. However, their potential as indicators for unfavorable treatment outcomes remains uncertain.
UNASSIGNED: This study was conducted within a well-characterized cohort comprising newly diagnosed patients with drug-sensitive pulmonary TB, confirmed through sputum smear and culture positivity. Our objective was to elucidate the TB antigen-stimulated cytokine profile at pre-treatment and at 2 months into anti-TB treatment (ATT) in patients with unfavorable treatment outcomes (cases, n = 27) in comparison to recurrence-free, microbiologically cured controls (n = 31). Whole blood was stimulated with TB antigens using the QuantiFERON In-tube gold method, and plasma supernatants were subjected to a panel of 14 cytokine measurements.
UNASSIGNED: In our study, pre-treatment analysis revealed that eight cytokines (IL-2, IFN-γ, TNF-α, IL-6, IL-10, IL-17A, IL-18, and GM-CSF) were significantly elevated at baseline in cases compared to cured controls, both in unstimulated conditions and following TB antigen (CFP10, ESAT6, and TB7.7) stimulation. A similar pattern was observed at the 2-month mark of ATT, with eight cytokines (IL-2, IL-10, IL-13, IFN-γ, IL-6, IL-12p70, IL-17A, and TNF-α) showing significant differences between the groups. Importantly, no variations were detected following mitogen stimulation, underscoring that these distinctive immune responses are primarily driven by TB-specific antigens.
UNASSIGNED: Our findings indicate that individuals with unfavorable TB treatment outcomes display a characteristic cytokine profile distinct from TB-cured patients, even before commencing ATT. Therefore, the levels of specific cytokine pre-treatment and at the 2-month point in the course of treatment may serve as predictive immune markers for identifying individuals at risk of unfavorable TB treatment outcomes, with these responses being predominantly influenced by TB-specific antigens.
摘要:
结核病(TB)治疗结果的评估主要依赖于痰培养转化状态。加强治疗管理,确定可预测不良结局的非基于痰的生物标志物至关重要.细胞因子作为活动性TB的诊断生物标志物被广泛研究。然而,它们作为不良治疗结果指标的潜力仍不确定.
这项研究是在一个特征明确的队列中进行的,该队列包括新诊断的药物敏感性肺结核患者,通过痰涂片和培养阳性证实。我们的目标是在治疗前和抗结核治疗(ATT)2个月后阐明结核病抗原刺激的细胞因子谱。n=27)与无复发相比,微生物固化对照(n=31)。使用QuantiFERON管内金方法,用TB抗原刺激全血,和血浆上清液进行一组14个细胞因子测量。
在我们的研究中,治疗前分析表明,八种细胞因子(IL-2,IFN-γ,TNF-α,IL-6,IL-10,IL-17A,IL-18和GM-CSF)在基线时与治愈的对照组相比显着升高,在未刺激的条件下和在TB抗原(CFP10,ESAT6和TB7.7)刺激下。在ATT的2个月标记处观察到类似的模式,与八种细胞因子(IL-2,IL-10,IL-13,IFN-γ,IL-6,IL-12p70,IL-17A,和TNF-α)显示两组之间的显着差异。重要的是,丝裂原刺激后没有检测到变化,强调这些独特的免疫应答主要由TB特异性抗原驱动。
我们的研究结果表明,结核病治疗结果不利的个体表现出与结核病治愈患者不同的特征性细胞因子谱。甚至在开始ATT之前。因此,治疗前和治疗过程中2个月时的特定细胞因子水平可作为预测免疫标志物,用于识别有不良结核病治疗结局风险的个体。这些反应主要受TB特异性抗原的影响。
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