UBC Faculty Research and Publications

Th17/Treg ratio derived using DNA methylation analysis discriminates allergen-induced early from dual… Singh, Amrit; Yamamoto, Masatsugu; Ruan, Jian; Choi, Jung Y; Gauvreau, Gail M; O’Byrne, Paul M; Olek, Sven; Hoffmueller, Ulrich; Carlsten, Christopher; FitzGerald, J M; Boulet, Louis-Philippe; Tebbutt, Scott J Mar 3, 2014

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MEETING ABSTRACT Open AccessTh17/Treg ratio derived using DNA methylationanalysis discriminates allergen-induced early fromdual asthmatic responsesAmrit Singh1*, Masatsugu Yamamoto1, Jian Ruan1, Jung Young Choi1, Gail M Gauvreau2, Paul M O’Byrne2,Sven Olek3, Ulrich Hoffmueller3, Christopher Carlsten4, J Mark FitzGerald4, Louis-Philippe Boulet5, Scott J Tebbutt1From Canadian Society of Allergy and Clinical Immunology Annual Scientific Meeting 2013Toronto, Canada. 3-6 October 2013BackgroundAtopic allergic asthmatic individuals experience acutebronchoconstriction (early response) upon allergenexposure. Several hours after the initial exposure, someindividuals exhibit a chronic late phase (dual responders,DRs) whereas others do not (early responders, ERs). Thepurpose of this study is to determine changes in Th17and regulatory T (Treg) cell numbers and their asso-ciated gene expression profiles in whole blood betweenallergen-induced ERs and DRs.Methods14 participants with mild, atopic asthma (8 ERs and6 DRs) underwent a cat allergen inhalation challenge aspart of the AllerGen Clinical Investigator Collaborative.Whole blood was collected immediately prior to challenge(pre) and 2 hours post-challenge. DNA methylation ana-lysis was used to measure the frequency of Th17,Treg, B and T cells (Epiontis, Germany). Whole bloodtranscriptome profiling was performed using AffymetrixGeneChip® Human Gene 1.0 ST Arrays. Statisticalanalysis was performed using R.ResultsSum of the T cell and B cell frequencies obtained usingthe methylation assays strongly correlated (r = 0.95) withthe lymphocyte frequency obtained using a hematolyzer.Allergen inhalation did not significantly (p>0.05) changeTh17, Treg, B and T cell counts between ERs and DRs.However, the Th17/Treg ratio was significantly (p=0.03)different between ERs and DRs post challenge. 199 genespositively correlated with Th17 cells at an FDR of 5%.463 genes positively correlated with Treg cells at anFDR of 5%. Th17 genes were inversely correlated withTreg genes.ConclusionsTh17/Treg ratio derived using DNA methylation analysisdiscriminates allergen-induced early from dual asthmaticresponses. The inverse correlation between Th17 genesand Treg genes may be indicative of the inflammatory orsuppressive phenotypes of these cells.Authors’ details1James Hogg Research Centre, St. Paul’s Hospital, University of BritishColumbia, Vancouver, British Columbia, V6Z 1Y6, Canada. 2Department ofMedicine, McMaster University, Hamilton, Ontario, L8S 4L8, Canada. 3EpiontisGmbH, Berlin, Germany. 4Vancouver Coastal Health Research Institute,Vancouver General Hospital, Vancouver, British Columbia, V5Z 1M9, Canada.5Centre de Pneumologie de L’Hopital, Université Laval, Sainte-Foy, Quebec,G1V 0B4, Canada.Published: 3 March 2014doi:10.1186/1710-1492-10-S1-A46Cite this article as: Singh et al.: Th17/Treg ratio derived using DNAmethylation analysis discriminates allergen-induced early from dualasthmatic responses. Allergy, Asthma & Clinical Immunology 201410(Suppl 1):A46.* Correspondence: amrit.singh@hli.ubc.ca1James Hogg Research Centre, St. Paul’s Hospital, University of BritishColumbia, Vancouver, British Columbia, V6Z 1Y6, CanadaFull list of author information is available at the end of the articleSingh et al. Allergy, Asthma & Clinical Immunology 2014, 10(Suppl 1):A46http://www.aacijournal.com/content/10/S1/A46 ALLERGY, ASTHMA & CLINICAL IMMUNOLOGY© 2014 Singh et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.


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