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oai:repisalud.isciii.es:20.500.12105/201212024-11-28T18:17:44Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16962col_20.500.12105_16963col_20.500.12105_16967

00925njm 22002777a 4500 dc Rodriguez-Cortez, Virginia C author del Pino-Molina, Lucia author Rodriguez-Ubreva, Javier author Ciudad, Laura author Gomez-Cabrero, David author Company, Carlos author Urquiza, Jose M author Tegner, Jesper author Rodriguez-Gallego, Carlos author Lopez-Granados, Eduardo author Ballestar, Esteban author 2015-06 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. Rodriguez-Cortez VC, Del Pino-Molina L, Rodriguez-Ubreva J, Ciudad L, Gomez-Cabrero D, Company C, et al. Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naive-to-memory B-cell transition. Nat Commun. 2015 Jun;6:7335. 10.1038/ncomms8335 2041-1723 Nature Communications http://hdl.handle.net/20.500.13003/10830 26081581 L604865275 2-s2.0-84935897991 http://hdl.handle.net/20.500.12105/20121 357172100018 Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naive-to-memory B-cell transition