Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/20121
Title
Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naive-to-memory B-cell transition
Author(s)
Date issued
2015-06
Citation
Rodriguez-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.
Language
Inglés
Document type
research article
Abstract
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.
MESH
Immunologic Memory | B-Lymphocytes | Case-Control Studies | DNA Methylation | Common Variable Immunodeficiency | Gene Expression Regulation | Humans | Twins, Monozygotic
DECS
Regulación de la Expresión Génica | Gemelos Monocigóticos | Humanos | Inmunodeficiencia Variable Común | Linfocitos B | Metilación de ADN | Memoria Inmunológica | Estudios de Casos y Controles
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