title: DNA methylation changes separate allergic patients from healthy controls and may reflect altered CD4+ T-cell population structure.
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 (N(patients) = 8, N(controls) = 8) and gene expression (N(patients) = 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 (N(patients) = 12, N(controls) = 12), but not by gene expression (N(patients) = 21, N(controls) = 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 (N(patients) = 35) and controls (N(controls) = 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.
authors.affiliation: The Centre for Individualized Medicine, Linköping University Hospital, Linköping University, Linköping, Sweden.
authors.forename: Colm E
authors.initials: CE
authors.lastname: Nestor
authors.affiliation: The Centre for Individualized Medicine, Linköping University Hospital, Linköping University, Linköping, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Barrenäs
authors.affiliation: The Centre for Individualized Medicine, Linköping University Hospital, Linköping University, Linköping, Sweden ; Department of Pediatrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: The Centre for Individualized Medicine, Linköping University Hospital, Linköping University, Linköping, Sweden.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lentini
authors.affiliation: The Centre for Individualized Medicine, Linköping University Hospital, Linköping University, Linköping, Sweden.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: The Centre for Individualized Medicine, Linköping University Hospital, Linköping University, Linköping, Sweden.
authors.forename: Sören
authors.initials: S
authors.lastname: Bruhn
authors.affiliation: Mathematical Sciences, Chalmers University of Technology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Rebecka
authors.initials: R
authors.lastname: Jörnsten
authors.affiliation: Department of Electrical Engineering and Computer Science, University of Tennessee, Knoxville, Tennessee, United States of America.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Langston
authors.affiliation: National Institute for Computational Sciences, University of Tennessee, Knoxville, Tennessee, United States of America.
authors.forename: Gary
authors.initials: G
authors.lastname: Rogers
authors.affiliation: The Centre for Individualized Medicine, Linköping University Hospital, Linköping University, Linköping, Sweden.
authors.forename: Mika
authors.initials: M
authors.lastname: Gustafsson
authors.affiliation: The Centre for Individualized Medicine, Linköping University Hospital, Linköping University, Linköping, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Benson
mesh_terms: D000328:Adult; D000485:Allergens / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D015870:Gene Expression; D015894:Genome, Human; D006801:Humans; D057089:Pathology, Molecular; D011058:Pollen / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics* / Q000276:immunology / Q000473:pathology
chemical_list: D000485:Allergens