Diver Sarah, Sridhar Sriram, Khalfaoui Latifa C, Russell Richard J, Emson Claire, Griffiths Janet M, de Los Reyes Melissa, Yin Da, Colice Gene, Brightling Christopher E
Institute for Lung Health, Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester, United Kingdom.
Translational Sciences, Early Oncology, Oncology R&D, Gaithersburg, Md.
J Allergy Clin Immunol. 2022 Oct;150(4):830-840. doi: 10.1016/j.jaci.2022.04.024. Epub 2022 May 7.
Understanding how asthma biomarkers relate to gene expression signatures could help identify drivers of pathogenesis.
This post hoc exploratory analysis of the phase II tralokinumab trial MESOS (ClinicalTrials.gov identifier NCT02449473) aimed to profile baseline airway inflammation in patients with moderate-to-severe asthma.
The T2 and T17 gene expression signatures, 3-gene mean and 5-gene mean, were calculated through transcriptomic analysis of baseline bronchial brushing samples. Clustering analysis using these signatures identified 3 distinct inflammatory subgroups: T2/T17 (n = 33), T2/T17 (n = 10), and T2/T17 (n = 27).
Fractional exhaled nitric oxide (Feno) levels were highest for T2/T17 and lowest for T2/T17 (median = 52.0 [range 42.5-116.3] and median = 18.8 [range 6.6-128.6] ppb, respectively; P = .003). High Feno levels were strongly correlated with high T2 gene expression (Spearman ρ = 0.5537; P < .001). Individual genes differentially expressed in patients with elevated levels of Feno, blood and bronchial submucosal eosinophil counts, and IgE level were explored, with cystatin SN (CST1) being the most upregulated gene in all subgroups (4.49- to 34.42-fold upregulation across clinically defined subgroups with high biomarker expression).
Feno level may be useful to differentiate patients with T2 or T17 gene expression. Elevated Feno levels are associated with high CST1 expression.
了解哮喘生物标志物与基因表达特征之间的关系有助于确定发病机制的驱动因素。
对II期曲罗芦单抗试验MESOS（ClinicalTrials.gov标识符NCT02449473）进行的这项事后探索性分析旨在描述中重度哮喘患者的基线气道炎症情况。
通过对基线支气管刷检样本进行转录组分析，计算T2和T17基因表达特征、3基因均值和5基因均值。使用这些特征进行聚类分析，确定了3个不同的炎症亚组：T2/T17（n = 33）、T2/T17（n = 10）和T2/T17（n = 27）。
T2/T17的呼出一氧化氮分数（Feno）水平最高，T2/T17最低（中位数分别为52.0[范围42.5 - 116.3]和中位数 = 18.8[范围6.6 - 128.6] ppb；P = .003）。高Feno水平与高T2基因表达密切相关（Spearman ρ = 0.5537；P < .001）。研究了在Feno水平升高、血液和支气管黏膜下嗜酸性粒细胞计数以及IgE水平升高的患者中差异表达的个体基因，胱抑素SN（CST1）是所有亚组中上调最明显的基因（在具有高生物标志物表达的临床定义亚组中上调4.49至34.42倍）。
Feno水平可能有助于区分具有T2或T17基因表达的患者。Feno水平升高与CST1高表达相关。
