UBC Faculty Research and Publications

Functional genomics of the peripheral blood response to allergen inhalation challenge Kam, Sarah H; Ruan, Jian; Gauvreau, Gail M; O'Byrne, Paul M; FitzGerald, J M; Tebbutt, Scott J Nov 26, 2010

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POSTER PRESENTATION Open AccessFunctional genomics of the peripheral bloodresponse to allergen inhalation challengeSarah HY Kam1, Jian Ruan1, Gail M Gauvreau2, Paul M O’Byrne2, J Mark FitzGerald3, Scott J Tebbutt1*From AllerGen NCE Inc.’s Fifth Annual Research Conference: Innovation from Cell to SocietyQuébec City, QC, Canada. 7-9 February 2010Objective/purposeIn asthmatic individuals, airway narrowing representsthe early phase of the asthmatic response to allergeninhalation challenge, occurring within thirty minutes [1].In 50-60% of allergic asthmatic adults, the earlyresponse is followed by the late phase asthmaticresponse, usually starting between 3-4 hours after aller-gen inhalation challenge [2], and characterized mainlyby cellular inflammation of the airway [3]. The pathwaysleading to the late response are not completely under-stood. Understanding these pathways is important forevaluating allergic diseases such as asthma. In contrastto the more transient isolated early response, develop-ment of the late response is associated with the hall-mark inflammatory features of chronic allergic disease.MethodsNine adult subjects participating in ethically approvedallergen challenge studies were recruited followinginformed consent. Inclusion criteria included non-smo-kers with stable, mild to moderate atopic asthma, free ofother lung diseases. Subjects developing either an iso-lated early asthmatic response (≥20% drop in FEV1within 2 hours) or the dual asthmatic response (earlyresponse + ≥15% drop in FEV1 between 3-7 hours)were studied. Peripheral blood was drawn just prior toinhalation challenge and 2-3 hours post-challenge. Geneexpression analysis was performed using AffymetrixGeneChip® microarrays.Findings1783 genes were differentially expressed between pre-and post-inhalation challenge (p ≤ 0.01). 364 genesremained significant at an FDR of 10%. Within this set,the DNAJC1 gene (p = 7.2e-5) has been previously iden-tified in a GWAS (genome-wide association study) asassociated with asthma. Gene ontology showed per-turbed activity in immune system process, mast cellsecretory granules and immunoglobulin biosynthesis.DeliverablesThe peripheral blood transcriptome was perturbedbetween pre-allergen inhalation challenge and 2-3 hourspost-challenge, with a focus on immunological func-tions. DNAJC1 was identified to be a gene for possiblefurther investigation. Additional recruitment of subjectsis underway to identify more specific biological path-ways that may be relevant to the onset of the late asth-matic response.RelevanceThis research will act as an initial step in identifyinggenes and pathways that may be involved in the moreclinically severe late asthmatic response that follows theearly response in more than half of the asthmatic popu-lation. The discovery of these biological pathways willallow for a better understanding of why some indivi-duals develop a dual response instead of an isolatedearly response. It will also indicate potential therapeutictargets that can be utilized to minimize the late asth-matic response, leading to better treatments for peoplewith asthma and other allergies.AcknowledgementsWe would like to thank the research participants for their involvement inthis project. This research is made possible by financial support fromAllerGen NCE.Author details1UBC James Hogg Research Centre, St. Paul’s Hospital, University of BritishColumbia, Vancouver, BC, V6Z 1Y6, Canada. 2Department of Medicine,* Correspondence: scott.tebbutt@hli.ubc.ca1UBC James Hogg Research Centre, St. Paul’s Hospital, University of BritishColumbia, Vancouver, BC, V6Z 1Y6, CanadaFull list of author information is available at the end of the articleKam et al. Allergy, Asthma & Clinical Immunology 2010, 6(Suppl 3):P3http://www.aacijournal.com/content/6/S3/P3 ALLERGY, ASTHMA & CLINICAL IMMUNOLOGY© 2010 Kam et al; licensee BioMed Central Ltd.McMaster University, Hamilton, Ontario, L8N 3Z5, Canada. 3Centre for LungHealth, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada.Published: 26 November 2010References1. Gauvreau GM, Evans MY: Allergen inhalation challenge: a human modelof asthma exacerbation. Contrib Microbiol 2007, 14:21-32.2. Robertson DG, Kerigan AT, Hargreave FE, Chalmers R, Dolovich J: Lateasthmatic responses induced by ragweed pollen allergen. J Allergy ClinImmunol 1974, 54(4):244-254.3. Cieslewicz G, Tomkinson A, Adler A, Duez C, Schwarze J, Takeda K,Larson KA, Lee JJ, Irvin CG, Gelfand EW: The late, but not early, asthmaticresponse is dependent on IL-5 and correlates with eosinophil infiltration.J Clin Invest 1999, 104(3):301-308.doi:10.1186/1710-1492-6-S3-P3Cite this article as: Kam et al.: Functional genomics of the peripheralblood response to allergen inhalation challenge. Allergy, Asthma &Clinical Immunology 2010 6(Suppl 3):P3.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitKam et al. Allergy, Asthma & Clinical Immunology 2010, 6(Suppl 3):P3http://www.aacijournal.com/content/6/S3/P3Page 2 of 2


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