Peripheral blood gene expression changes during allergen inhalation challenge in atopic asthmatic individuals

Sarah H Y Kam, Amrit Singh, Jian Qing He, Jian Ruan, Gail M. Gauvreau, Paul M. O'Byrne, J. Mark Fitzgerald, Scott J. Tebbutt

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Objectives. (1) To investigate the effects of globin mRNA depletion in detecting differential gene expression in peripheral blood and (2) to investigate changes in peripheral blood gene expression in atopic asthmatic individuals undergoing allergen inhalation challenge. Methods. Asthmatic subjects (2060 years of age, with stable, mild allergic asthma, n = 9) underwent allergen inhalation challenges. All had an early asthmatic response of ≥20% fall in forced expiratory volume in 1 second. Blood was collected immediately prior to and 2 hours after allergen challenge using PAXgene tubes (n = 4) and EDTA tubes (n = 5). Aliquots of the PAXgene blood samples were subjected to globin reduction (PAX-GR). Transcriptome analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST arrays. Data were preprocessed using factor analysis for robust microarray summarization and analyzed using linear models for microarrays. Pathway analyses were performed using Ingenuity Pathway Analysis. Results. Globin reduction uncovered probe sets of lower abundance. However, it significantly reduced the ability to detect differentially expressed genes (DEGs) when compared to non-globin-reduced PAXgene samples (PAX-NGR). Combined transcriptional analysis of four PAX-NGR and five EDTA sample pairs identified 1595 DEGs associated with allergen inhalation challenge (false discovery rate ≤ 5%), with the top-ranked network of perturbed biological functions consisting of inflammatory response, cellular movement, and immune cell trafficking. Conclusions. While we have demonstrated a diminished ability to detect DEGs after globin reduction, we have nevertheless identified significant changes in the peripheral blood transcriptome of people with mild asthma 2 hours after allergen inhalation challenge. © 2012 Informa Healthcare USA, Inc.
    Original languageEnglish
    Pages (from-to)219-226
    Number of pages7
    JournalJournal of Asthma
    Volume49
    Issue number3
    DOIs
    Publication statusPublished - Apr 2012

    Keywords

    • Factor analysis for robust microarray summarization
    • Globin mRNA reduction
    • Linear models for microarrays
    • Microarray analysis

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