Abstract

Peripheral Whole Blood Transcriptomes of Asthmatic Individuals Undergoing Allergen Inhalation Challenge

Scott Tebbutt, Associate Professor, University of British Columbia

Asthma is a chronic condition affecting 300 million people worldwide, and remains poorly understood due to its complexity and heterogeneity. Two particularly important subtypes of asthma can be identified via a human experimental model of allergen exposure in which sensitized individuals undergo allergen inhalation challenge (AIC). Individuals with allergic asthma respond differently, but reproducibly, to this allergen challenge. Some develop an isolated early response (ER) while others also go on to develop a late response (dual responders; DR). It is not understood why late responses do not develop in all sensitized subjects. Since it is the consequences of the late asthmatic response that are believed to contribute to chronic airway inflammation and uncontrolled disease it is important to identify molecular mechanisms and biomarkers that can discriminate between these different response types. We have profiled the peripheral whole blood transcriptomes of 17 ER individuals and 18 DR individuals undergoing AIC. Illumina rRNA/globin-depleted stranded cDNA libraries were generated from total cellular RNA, and paired-end HiSeq sequencing was performed on each library. Approx. 26 million paired reads were obtained per sample. Differential expression analysis pre-AIC revealed 464 differentially expressed RefSeq transcripts at an FDR of 10% (165 over- and 299 under-expressed in DRs). Top MetaCore pathways (FDR<0.1%) included: Blood coagulation_GPCRs in platelet aggregation & Cell adhesion_Integrin inside-out signaling.