Gene Expression Networks of Allergic Asthma As Characterized By IgE Levels Among Costa Rican Children

Rationale: Allergic asthma remains the most common subtype of asthma, and novel biological therapies targeting immunoglobulin E (IgE)-mediated pathways have widened clinical treatment options for the disease. Using IgE as a disease biomarker, we used gene expression network analysis to identify novel genes involved in the pathophysiology of allergic asthma.

Methods: We examined gene expression profiles from a cross-sectional study of 328 Costa Rican children with asthma, ages 6 to 12 years. After performing weighted gene co-expression network analysis (WGCNA) on 25,060 genes, we used multivariate regression to test associations of core network modules with total IgE, adjusting for age and gender. We then used pathway enrichment analysis (GeneOntology and WebGestalt) to identify key biological pathways underlying the associated modules.

Results: We identified two highly significant modules: a “dark red”-labeled module positively associated with IgE (p < 0.001) and a “dark turquoise” module negatively associated with IgE (p = 0.002). The “dark red” module was enriched for the “calmodulin-dependent protein kinase activity” pathway (CAMK1, DAPK2, EEF2K) (p = 0.0096). The “dark turquoise” module showed down-regulation of pathways involving “B cell receptor signaling” (CD19, BLK, CD79A, CD79B, FCRL5) (p = 0.002).

Conclusions: These results suggest that there exist gene expression profiles of pediatric allergic asthma related to levels of total IgE—specifically, pathways mediating calmodulin-dependent protein kinase activity. As such pathways are involved in smooth muscle contraction and have been implicated in the pathophysiology of asthma, they may represent novel therapeutic targets.