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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/126092
Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naı¨ve-to-memory B-cell transition
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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.
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RODRÍGUEZ CORTEZ, Virginia carolina, PINO MOLINA, Lucía 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. Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naı¨ve-to-memory B-cell transition. _Nature Communications_. 2015. Vol. 6. [consulta: 5 de maig de 2026]. [Disponible a: https://hdl.handle.net/2445/126092]