Abstract

Asthma is a chronic inflammatory disorder associated with airway hyper-responsiveness. Although a number of studies have investigated asthma at the molecular level, the molecular immune signatures associated with asthma severity or with the response to corticosteroids are still being unraveled. The present study integrated four asthma-related gene expression datasets from the Gene Expression Omnibus and identified immune-gene signatures associated with asthma development, severity, or response to treatment. Normal and mild asthmatic patients clustered separately from the severe asthma group, suggesting substantial progression-related changes in gene expression. Pathway analysis of up-regulated severe asthma-related genes identified multiple cellular processes, such as polymorphism, T-cell development, and transforming growth factor-β signaling. Comparing gene expression profiles of bronchoalveolar lavage cells in response to corticosteroid treatment, showed substantial reductions in genes related to the inflammatory response, including tumor necrosis factor signaling in the corticosteroid sensitive versus resistant patients, suggesting a defective immune response to corticosteroids. The data highlight the multifactorial nature of asthma, but revealed no significant overlap with the gene expression profiles from different datasets interrogated in current studies. The presented profile suggests that genes involved in asthma progression are different from those involved in the response to corticosteroids and this could affect the clinical management of different groups of patients with asthma.

Highlights

  • Asthma is a chronic inflammatory disorder characterized by reversible airway obstruction and hyperresponsiveness [1]

  • We analyzed the GSE27876 series comparing peripheral blood cells from mild and severe asthma that were selected from patients classified into the asthma treatment step 4, based on the criteria described in the Global Initiative for Asthma (GINA) compared with those from normal subjects [10]

  • Further differentially expressed genes were detected in patients with severe asthma, with 137 up-regulated and 69 down-regulated genes compared with normal individuals (Figure 1B,C)

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Summary

Introduction

Asthma is a chronic inflammatory disorder characterized by reversible airway obstruction and hyperresponsiveness [1]. Many patients will have a genetic predisposition to developing asthma. The initial description of asthma involves identifying clinical, physiological, and cellular parameters. Clinical characteristics include age at asthma onset, allergen type, family history, or even the degree of airway obstruction; the familiar physiological features, such as wheezing, shortness of breath, and coughing; and cellular parameters [2]. These characteristics alone are not enough to identify the importance of a specific pathological process or improve the treatment of patients with asthma

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