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

Author

Listed:
  • Virginia C. Rodríguez-Cortez

    (Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL))

  • Lucia del Pino-Molina

    (University Hospital La Paz
    Physiopathology of Lymphocytes in Immunodeficiencies Group, IdiPAZ Institute for Health Research)

  • Javier Rodríguez-Ubreva

    (Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL))

  • Laura Ciudad

    (Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL))

  • David Gómez-Cabrero

    (Unit of Computational Medicine, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, L8:05)

  • Carlos Company

    (Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL))

  • José M. Urquiza

    (Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL))

  • Jesper Tegnér

    (Unit of Computational Medicine, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, L8:05)

  • Carlos Rodríguez-Gallego

    (University Hospital Son Espases, Carretera de Valldemossa, 79, 07120 Palma de Mallorca, Spain)

  • Eduardo López-Granados

    (University Hospital La Paz
    Physiopathology of Lymphocytes in Immunodeficiencies Group, IdiPAZ Institute for Health Research)

  • Esteban Ballestar

    (Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL))

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.

Suggested Citation

  • Virginia C. Rodríguez-Cortez & Lucia del Pino-Molina & Javier Rodríguez-Ubreva & Laura Ciudad & David Gómez-Cabrero & Carlos Company & José M. Urquiza & Jesper Tegnér & Carlos Rodríguez-Gallego & Edua, 2015. "Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naïve-to-memory B-cell transition," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8335
    DOI: 10.1038/ncomms8335
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