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Article

DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life

1
Department of Clinical Science and Education, Karolinska Institutet, and Sachs’ Children and Youth Hospital, Södersjukhuset, SE-118 83 Stockholm, Sweden
2
Institute for Immunological Research, University of Cartagena, 130014 Cartagena, Colombia
3
Department of Biology, University of Naples Federico II, 80138 Napoli, Italy
4
Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland
5
Institute of Biosciences and Medical Technologies (BioMediTech), Tampere University, 33520 Tampere, Finland
6
Department of Political Sciences, University of Pisa, 56126 Pisa, Italy
7
Department of Medicine Solna, Translational Immunology Unit, Karolinska Institutet, SE-171 77 Stockholm, Sweden
8
Stockholm Bioinformatics Center, Department of Biochemistry and Biophysics, Stockholm University, Science for Life Laboratory, SE-17121 Solna, Sweden
9
Institute of Computational Biology, Helmholtz Center Munich, 85764 Neuherberg, Germany
10
Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden
11
Section of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
12
Groningen Research Institute of Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
13
Department of Biosciences and Nutrition, Karolinska Institutet, SE-171 77 Stockholm, Sweden
14
Department of Women’s and Children’s Health, Karolinska Institutet, SE-171 77 Stockholm, Sweden
15
Folkhälsan Research Institute, Stem Cells and Metabolism Research Program, University of Helsinki, 00014 Helsinki, Finland
16
Institute of Biotechnology, University of Helsinki, FI-00014 Helsinki, Finland
17
Science for Life Laboratory, Karolinska Institutet, SE-171 65 Solna, Sweden
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
§
These authors contributed equally to this work as senior co-Authors.
Int. J. Mol. Sci. 2021, 22(2), 801; https://doi.org/10.3390/ijms22020801
Received: 28 October 2020 / Revised: 22 December 2020 / Accepted: 23 December 2020 / Published: 14 January 2021
(This article belongs to the Special Issue Molecular Mechanisms of Allergy and Asthma)
DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle and Allergic Disease During INfancy) using the HumanMethylation450BeadChip (Illumina). PBMCs were obtained from the mothers during pregnancy and from their children in cord blood, at 2 years and 5Y. DNA methylation levels at each time point were compared between children with and without IgE sensitization to allergens at 5Y. For replication, CpG sites associated with IgE sensitization in ALADDIN were evaluated in whole blood DNA of 256 children, 4 years old, from the BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) cohort. We found 34 differentially methylated regions (DMRs) associated with IgE sensitization to airborne allergens and 38 DMRs associated with sensitization to food allergens in children at 5Y (Sidak p ≤ 0.05). Genes associated with airborne sensitization were enriched in the pathway of endocytosis, while genes associated with food sensitization were enriched in focal adhesion, the bacterial invasion of epithelial cells, and leukocyte migration. Furthermore, 25 DMRs in maternal PBMCs were associated with IgE sensitization to airborne allergens in their children at 5Y, which were functionally annotated to the mTOR (mammalian Target of Rapamycin) signaling pathway. This study supports that DNA methylation is associated with IgE sensitization early in life and revealed new candidate genes for atopy. Moreover, our study provides evidence that maternal DNA methylation levels are associated with IgE sensitization in the child supporting early in utero effects on atopy predisposition. View Full-Text
Keywords: ALLADIN; allergens; atopy; BAMSE; DNA methylation; IgE sensitization; epigenetics; maternal effects ALLADIN; allergens; atopy; BAMSE; DNA methylation; IgE sensitization; epigenetics; maternal effects
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MDPI and ACS Style

Acevedo, N.; Scala, G.; Merid, S.K.; Frumento, P.; Bruhn, S.; Andersson, A.; Ogris, C.; Bottai, M.; Pershagen, G.; Koppelman, G.H.; Melén, E.; Sonnhammer, E.; Alm, J.; Söderhäll, C.; Kere, J.; Greco, D.; Scheynius, A. DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life. Int. J. Mol. Sci. 2021, 22, 801. https://doi.org/10.3390/ijms22020801

AMA Style

Acevedo N, Scala G, Merid SK, Frumento P, Bruhn S, Andersson A, Ogris C, Bottai M, Pershagen G, Koppelman GH, Melén E, Sonnhammer E, Alm J, Söderhäll C, Kere J, Greco D, Scheynius A. DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life. International Journal of Molecular Sciences. 2021; 22(2):801. https://doi.org/10.3390/ijms22020801

Chicago/Turabian Style

Acevedo, Nathalie, Giovanni Scala, Simon Kebede Merid, Paolo Frumento, Sören Bruhn, Anna Andersson, Christoph Ogris, Matteo Bottai, Göran Pershagen, Gerard H. Koppelman, Erik Melén, Erik Sonnhammer, Johan Alm, Cilla Söderhäll, Juha Kere, Dario Greco, and Annika Scheynius. 2021. "DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life" International Journal of Molecular Sciences 22, no. 2: 801. https://doi.org/10.3390/ijms22020801

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