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Analyze whole-blood transcriptomes across severe asthma patients stratified by type-2 biomarkers and symptom control to identify molecular signatures related to persistent symptoms.

June 12, 2023Journal of Allergy and Clinical ImmunologyOpen Access

Blood transcriptomic signature in type-2 biomarker-low severe asthma and asthma control

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Analyze whole-blood transcriptomes across severe asthma patients stratified by type-2 biomarkers and symptom control to identify molecular signatures related to persistent symptoms.
Bulk RNA sequencing was performed on 738 whole-blood samples collected at baseline, week 24, and week 48 from 301 participants in a randomized clinical trial of corticosteroid optimization.
Unsupervised clustering, differential gene expression, and pathway analyses were conducted, evaluating gene expression profiles with and without adjustment for oral corticosteroid (OCS) use.
Unsupervised clustering revealed two clusters, where cluster 2 exhibited low blood eosinophils, high symptom burden, and greater frequency of OCS use, generating 2,960 differentially expressed genes (DEGs), of which 627 remained after subtracting OCS-specific signatures.
Pathway enrichment identified dolichyl-diphosphooligosaccharide biosynthesis and RNA polymerase I complex assembly among significantly altered processes.
No stable DEGs were associated with high symptom burden in type-2 biomarker-low severe asthma, whereas elevated type-2 biomarkers yielded multiple DEGs, including 15 genes consistently upregulated across all time points regardless of symptom control.

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Implication

Randomized trial secondary analysis uncovers distinct transcriptomic signatures for oral corticosteroids and high type-2 biomarkers, suggesting symptom drivers in low-type-2 asthma remain elusive.

Cite This Study

Zeng et al. (2023) studied this question.

synapsesocial.com/papers/6a8316e2c4b5dbf8331f2cc8 https://doi.org/10.1016/j.jaci.2023.05.023

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Implication

Randomized trial secondary analysis uncovers distinct transcriptomic signatures for oral corticosteroids and high type-2 biomarkers, suggesting symptom drivers in low-type-2 asthma remain elusive.

Blood transcriptomic signature in type-2 biomarker-low severe asthma and asthma control

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Discussion

Implication

Cite This Study

Blood transcriptomic signature in type-2 biomarker-low severe asthma and asthma control

Key Points

Discussion

Implication

Cite This Study

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