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Asthma in youths: Insights from gene expression patterns

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Created On: 22/04/2025

Asthma is not a one-size-fits-all disease—immune pathways differ across individuals.

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Key take away

Most youths (age 6–20 years) with asthma have T2-low endotypes, with allergen sensitization common in all endotypes.

Background

Asthma is not a one-size-fits-all disease—immune pathways differ across individuals. In asthma, T helper 17 (T17) and T helper 2 (T2) cells, both CD4+ T cell subtypes, play distinct roles. Understanding these immune-driven endotypes in diverse youth populations could pave the way for precision therapies. Hence, this study explored asthma endotypes in youths by examining nasal epithelial transcriptomic profiles.

Method

This study examined nasal mucosa samples from 3 cohorts of school-aged youths battling asthma:

STAR (Stress and Treatment Response in Puerto Rican and African American Children with Asthma; 156 youths; mean age 14.2 years)
EVA-PR (Epigenetic Variation and Childhood Asthma in Puerto Ricans; 237 youths; mean age 15.4 years)
VDKA (Vitamin D Kids Asthma; 66 youths; mean age 10.3 years)

The primary endpoint ascertained was nasal epithelial transcription profiles of three T2 and five T17 pathway genes. In all the assessments, the lung function, blood eosinophil counts, clinical characteristics, and total and allergen-specific immunoglobulin E (IgE) were determined across the transcriptomic profiles.

Result

In this cross-sectional study, female participants comprised 41% to 53.2% of each study. The primary racial/ethnic groups were Puerto Rican (100%) in EVA-PR and Black or African American (71.8% in STAR, 57.6% in VDKA). In total, 3 transcriptomic profiles were identified:

T2HIGH (high T2 expression): 23%–29% of volunteers
T17HIGH (high T17 expression): 35%–47% of volunteers
T2LOW/T17LOW (decreased expression of both pathways): 30%–38% of volunteers

Median total IgE and blood eosinophil counts were elevated in the T2HIGH profile than in T2LOW (IgE: 584–869 vs. 105–382 IU/mL; eosinophils: 343–560 vs. 164–413 cells/mL). Across all profiles, a minimum of 50% subjects exhibited one or more positive allergen-targeted IgEs. Meta-analysis identified 3,516 differentially expressed genes in T2HIGH and 2,494 in T17HIGH. T17HIGH was linked to interleukin (IL)-17 and neutrophil signaling pathways, while T2HIGH was related to IL-13 signaling pathways.

Conclusion

Across 3 studies of racially and ethnically minoritized youths suffering from asthma, nasal transcriptomic profiles identified T2-high, T17-high, and T2-low/T17-low endotypes in comparable proportions. T2-low asthma was most prevalent, and allergen sensitization was common across all endotypes.