Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naı¨ve-to-memory B-cell transition

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 disor...

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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/126092
Acceso en línea:https://hdl.handle.net/2445/126092
Access Level:acceso abierto
Palabra clave:Immunodeficiència
ADN
Cèl·lules B
Immunodeficiency
DNA
B cells
Descripción
Sumario: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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