Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naive-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: Rodriguez-Cortez, Virginia C., del Pino-Molina, Lucia, Rodriguez-Ubreva, Javier, Ciudad, Laura, Gomez-Cabrero, David, Company, Carlos, Urquiza, Jose M., Tegner, Jesper, Rodriguez-Gallego, Carlos, Lopez-Granados, Eduardo, Ballestar, Esteban
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/10830
Acceso en línea:https://hdl.handle.net/20.500.13003/10830
Access Level:acceso abierto
Palabra clave:B-Lymphocytes
Twins, Monozygotic
Immunologic Memory
Gene Expression Regulation
Humans
Case-Control Studies
DNA Methylation
Common Variable Immunodeficiency
Estudios de Casos y Controles
Regulación de la Expresión Génica
Gemelos Monocigóticos
Humanos
Inmunodeficiencia Variable Común
Linfocitos B
Metilación de ADN
Memoria Inmunológica
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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