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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 <jats:italic>PIK3CD<\/jats:italic>, <jats:italic>BCL2L1<\/jats:italic>, <jats:italic>RPS6KB2<\/jats:italic>, <jats:italic>TCF3<\/jats:italic> and <jats:italic>KCNN4<\/jats:italic>. 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.<\/jats:p>","DOI":"10.1038\/ncomms8335","type":"journal-article","created":{"date-parts":[[2015,6,17]],"date-time":"2015-06-17T10:33:07Z","timestamp":1434537187000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during na\u00efve-to-memory B-cell transition"],"prefix":"10.1038","volume":"6","author":[{"given":"Virginia C.","family":"Rodr\u00edguez-Cortez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"del Pino-Molina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Rodr\u00edguez-Ubreva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ciudad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"G\u00f3mez-Cabrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Company","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"Urquiza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Tegn\u00e9r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Rodr\u00edguez-Gallego","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"L\u00f3pez-Granados","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Ballestar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,6,17]]},"reference":[{"key":"BFncomms8335_CR1","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/nri1713","volume":"5","author":"C Cunningham-Rundles","year":"2005","unstructured":"Cunningham-Rundles, C. & Ponda, P. 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