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DNA Methylation Changes Separate Allergic Patients from Healthy Controls and May Reflect Altered CD4⁺ T-Cell Population Structure

Journal article
Authors C.E. Nestor
Fredrik Barrenäs
Hui Wang
A. Lentini
H. Zhang
Sören Bruhn
Rebecka Jörnsten
M.A. Langston
G. Rogers
M. Gustafsson
M. Benson
Published in PLoS Genetics
Volume 10
Issue 1
ISSN 1553-7390
Publication year 2014
Published at Department of Mathematical Sciences, Mathematical Statistics
Institute of Clinical Sciences, Department of Pediatrics
Language en
Links dx.doi.org/10.1371/journal.pgen.100...
https://gup.ub.gu.se/file/131841
Keywords DNA methylation, Epigenetics, Gene expression, Memory T cells, Methylation, Microarrays, Pollen, T cells
Subject categories Clinical Medicine

Abstract

Altered DNA methylation patterns in CD4+ T-cells indicate the importance of epigenetic mechanisms in inflammatory diseases. However, the identification of these alterations is complicated by the heterogeneity of most inflammatory diseases. Seasonal allergic rhinitis (SAR) is an optimal disease model for the study of DNA methylation because of its well-defined phenotype and etiology. We generated genome-wide DNA methylation (Npatients = 8, Ncontrols = 8) and gene expression (Npatients = 9, Ncontrols = 10) profiles of CD4+ T-cells from SAR patients and healthy controls using Illumina's HumanMethylation450 and HT-12 microarrays, respectively. DNA methylation profiles clearly and robustly distinguished SAR patients from controls, during and outside the pollen season. In agreement with previously published studies, gene expression profiles of the same samples failed to separate patients and controls. Separation by methylation (Npatients = 12, Ncontrols = 12), but not by gene expression (Npatients = 21, Ncontrols = 21) was also observed in an in vitro model system in which purified PBMCs from patients and healthy controls were challenged with allergen. We observed changes in the proportions of memory T-cell populations between patients (Npatients = 35) and controls (Ncontrols = 12), which could explain the observed difference in DNA methylation. Our data highlight the potential of epigenomics in the stratification of immune disease and represents the first successful molecular classification of SAR using CD4+ T cells.

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