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CD4+ T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases

Authors :
Tejaswi V. Badam
Sandra Hellberg
Ratnesh B. Mehta
Jeannette Lechner-Scott
Rodney A. Lea
Jorg Tost
Xavier Mariette
Judit Svensson-Arvelund
Colm E. Nestor
Mikael Benson
Göran Berg
Maria C. Jenmalm
Mika Gustafsson
Jan Ernerudh
Source :
Epigenetics, Vol 17, Iss 9, Pp 1040-1055 (2022)
Publication Year :
2022
Publisher :
Taylor & Francis Group, 2022.

Abstract

Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4+ T-cells in non-pregnant and pregnant women, during the 1st and 2nd trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2nd trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases. Abbreviations: BMIQ: beta-mixture quantile dilation; DMGs: differentially methylated genes; DMPs: differentially methylated probes; FE: fold enrichment; FDR: false discovery rate; GO: gene ontology; GWAS: genome-wide association studies; MDS: multidimensional scaling; MS: multiple sclerosis; PBMC: peripheral blood mononuclear cells; PBS: phosphate buffered saline; PPI; protein-protein interaction; RA: rheumatoid arthritis; SD: standard deviation; SLE: systemic lupus erythematosus; SNP: single nucleotide polymorphism; TH: CD4+ T helper cell; VIStA: diVIsive Shuffling Approach.

Details

Language :
English
ISSN :
15592294 and 15592308
Volume :
17
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Epigenetics
Publication Type :
Academic Journal
Accession number :
edsdoj.82fde3e3be1f4925b203e0997ce02cf5
Document Type :
article
Full Text :
https://doi.org/10.1080/15592294.2021.1982510