Distinct blood transcriptomic profiling underlying asthma establishment and exacerbation

Document Type

Article

Publication Date

3-1-2026

Keywords

Gene expression profiling; asthma exacerbation; controlled asthma; driver genes; drug repurposing; non-Hispanic Black; uncontrolled asthma

Publication Title

J Allergy Clin Immunol Glob

Abstract

BACKGROUND: Non-Hispanic Black individuals are disproportionately affected by asthma and severe asthma exacerbations. To elucidate asthma pathogenesis, it is essential to understand the dysregulated gene expression patterns linked to asthma status.

OBJECTIVE: We sought to characterize whole blood gene expression and molecular pathways associated with asthma progression in non-Hispanic Black individuals.

METHODS: RNA sequencing was performed on whole blood samples from individuals enrolled in the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE). Participants were categorized into 4 groups based on their clinical status. We characterized transcriptomic signatures specific to distinct disease states: one reflecting asthma establishment and another representing disease exacerbation. From these, we identified candidate biological processes enriched during each transition that are particularly relevant to asthma. Additionally, we pinpointed key molecular drivers and screened for drugs targeting these critical genes.

RESULTS: Compared with healthy control subjects, patients with controlled asthma showed upregulation of genes involved in intestinal IgA production, asthma-related pathways, and antigen processing and presentation. When compared with participants with uncontrolled asthma, individuals with an impending asthma exacerbation had upregulation of genes in pathways associated with Fcγ receptor-mediated phagocytosis, T(H)1/T(H)2 cell differentiation, and neutrophil extracellular trap formation. Using probabilistic causal analysis of these gene signatures, we identified IL6R, NUMB, and EMG1 as key driver genes in the time period preceding an asthma exacerbation. Our analysis revealed potential treatments to counteract these changes.

CONCLUSIONS: Blood gene expression profiling in non-Hispanic Black individuals revealed potential targets and preventive drug candidates for asthma exacerbations, providing new insights for the future treatments.

PubMed ID

41660047

Volume

5

Issue

2

First Page

100644

Last Page

100644

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