Publications 2015

​Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naïve-to-memory B-cell transition
V. Rodríguez-Cortez, L. Pino-Molina, J. Rodríguez-Ubreva, L. Ciudad, D. Gómez-Cabrero, C. Company, J. Urquiza, J. Tegnér, C. Rodríguez-Gallego, E. López-Granados, E. Ballestar
Nature Communications, Volume 6, Article number 7335, 2015
. Rodríguez-Cortez, L. Pino-Molina, J. Rodríguez-Ubreva, L. Ciudad, D. Gómez-Cabrero, C. Company, J. Urquiza, J. Tegnér, C. Rodríguez-Gallego, E. López-Granados, E. Ballestar
DNA; Gene expression; Germ cell; Memory; Methylation
2015
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.


DOI: 10.1038/ncomms8335

Monozygotic twins discordant for common variable immunodeficiency.pdfMonozygotic twins discordant for common variable immunodeficiency.pdf