期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 150, 期 4, 页码 830-840出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2022.04.024
关键词
Asthma; expression profiling
资金
- AstraZeneca
- National Institute for Health Research (NIHR), Respiratory Translational Research Collaboration and NIHR Biomedical Research Centers
This study analyzed baseline airway inflammation in patients with moderate-to-severe asthma and found that F-ENO levels may be associated with T2 or T17 gene expression, while elevated FENO levels are correlated with high CST1 expression.
Background: Understanding how asthma biomarkers relate to gene expression signatures could help identify drivers of pathogenesis. Objective: 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. Methods: 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(LOW)/T17(HIGH) (n = 33), T2(HIGH)/T17(LOW) (n = 10), and T2(LOW)/T17(LOW) (n = 27). Results: Fractional exhaled nitric oxide (F-ENO) levels were highest for T2(HIGH)/T17(LOW) and lowest for T2(LOW)/T17(HIGH) (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 rho = 0.5537; P <.001). Individual genes differentially expressed in patients with elevated levels of F-ENO, 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). Conclusion: F-ENO level may be useful to differentiate patients with T2 or T17 gene expression. Elevated FENO levels are associated with high CST1 expression.
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