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s41467-022-29450-x.pdf (9.84 MB)

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2022-04-01

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cc by (c) Rodríguez Ubreva, Javier et al, 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/185208

Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses

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https://doi.org/10.1038/s41467-022-29450-x

Resum

Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency. Here the authors perform single-cell omics analyses in CVID-discordant monozygotic twins and show epigenetic and transcriptional alterations associated with activation in memory B cells. Common variable immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency, displays impaired terminal B-cell differentiation and defective antibody responses. Incomplete genetic penetrance and ample phenotypic expressivity in CVID suggest the participation of additional pathogenic mechanisms. Monozygotic (MZ) twins discordant for CVID are uniquely valuable for studying the contribution of epigenetics to the disease. Here, we generate a single-cell epigenomics and transcriptomics census of naive-to-memory B cell differentiation in a CVID-discordant MZ twin pair. Our analysis identifies DNA methylation, chromatin accessibility and transcriptional defects in memory B-cells mirroring defective cell-cell communication upon activation. These findings are validated in a cohort of CVID patients and healthy donors. Our findings provide a comprehensive multi-omics map of alterations in naive-to-memory B-cell transition in CVID and indicate links between the epigenome and immune cell cross-talk. Our resource, publicly available at the Human Cell Atlas, gives insight into future diagnosis and treatments of CVID patients.

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Limfòcits, Epigenètica

Matèries (anglès)

Lymphocytes, Epigenetics

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

RODRÍGUEZ UBREVA, Javier, ARUTYUNYAN, Anna, BONDER, Marc jan, PINO MOLINA, Lucía del, CLARK, Stephen j., CALLE FABREGAT, Carlos de la, GARCÍA ALONSO, Luz, HANDFIELD, Louis françois, CIUDAD, Laura, ANDRÉS LEÓN, Eduardo, KRUEGER, Felix, CATALÀ MOLL, Francesc, RODRÍGUEZ CORTEZ, Virginia carolina, POLANSKI, Krzysztof, MAMANOVA, Lira, DONGEN, Stijn van, KISELEV, Vladimir yu., MARTÍNEZ SAAVEDRA, María t., HEYN, Holger, MARTÍN, Javier, WARNATZ, Klaus, LÓPEZ GRANADOS, Eduardo, RODRÍGUEZ GALLEGO, Carlos, STEGLE, Oliver, KELSEY, Gavin, VENTO TORMO, Roser, BALLESTAR TARÍN, Esteban. Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses. _Nature Communications_. 2022. [consulta: 31 de gener de 2026]. ISSN: 2041-1723. [Disponible a: https://hdl.handle.net/2445/185208]

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