Title:
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Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naı¨ve-to-memory B-cell transition
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Author:
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Rodríguez Cortez, Virginia Carolina; Pino Molina, Lucia Del; Rodríguez Ubreva, Javier; Ciudad, Laura; Gómez Cabrero, David; Company, Carlos; Urquiza, José M.; Tegnér, Jesper; Rodríguez Gallego, Carlos; López Granados, Eduardo; Ballestar Tarín, Esteban
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Abstract:
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Common variable immunodeficiency (CVID), the most frequent primary immunodeficiency characterized by loss of B-cell function, depends partly on genetic defects, and epigenetic changes are thought to contribute to its aetiology. Here we perform a high-throughput DNA methylation analysis of this disorder using a pair of CVID-discordant MZ twins and show predominant gain of DNA methylation in CVID B cells with respect to those from the healthy sibling in critical B lymphocyte genes, such as PIK3CD, BCL2L1, RPS6KB2, TCF3 and KCNN4. Individual analysis confirms hypermethylation of these genes. Analysis in naive, unswitched and switched memory B cells in a CVID patient cohort shows impaired ability to demethylate and upregulate these genes in transitioning from naive to memory cells in CVID. Our results not only indicate a role for epigenetic alterations in CVID but also identify relevant DNA methylation changes in B cells that could explain the clinical manifestations of CVID individuals. |
Subject(s):
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-Immunodeficiència -ADN -Cèl·lules B -Immunodeficiency -DNA -B cells |
Rights:
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cc by (c) Rodríguez-Cortez, Virginia C. et al., 2015
http://creativecommons.org/licenses/by/3.0/es/ |
Document type:
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Article Article - Published version |
Published by:
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Nature Publishing Group
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