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

Rodriguez-Cortez, Virginia Cdel Pino-Molina, LuciaRodriguez-Ubreva, JavierCiudad, LauraGomez-Cabrero, DavidCompany, CarlosUrquiza, Jose MTegner, JesperRodriguez-Gallego, CarlosLopez-Granados, EduardoBallestar, Esteban2024-07-042024-07-042015-06Rodriguez-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;6:7335.2041-1723http://hdl.handle.net/20.500.13003/10830http://hdl.handle.net/20.500.12105/20121Common 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.enghttp://creativecommons.org/licenses/by/4.0/Immunologic MemoryB-LymphocytesCase-Control StudiesDNA MethylationCommon Variable ImmunodeficiencyGene Expression RegulationHumansTwins, MonozygoticMonozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naive-to-memory B-cell transitionresearch articleAttribution 4.0 International260815816733510.1038/ncomms8335Nature Communicationsopen accessRegulación de la Expresión GénicaGemelos MonocigóticosHumanosInmunodeficiencia Variable ComúnLinfocitos BMetilación de ADNMemoria InmunológicaEstudios de Casos y Controles2-s2.0-84935897991357172100018L604865275