Journal
NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-29450-x
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Funding
- Spanish Ministry of Science and Innovation [PID2020-117212RB-I00/AEI/10.13038/501100011033]
- Instituto de Salud Carlos III (ISCIII) [AC18/00057]
- i-PAD project (ERARE European Union program)
- Jeffrey Modell Foundation
- Wellcome Sanger core funding [WT206194]
- Chan Zuckerberg Initiative [2020-216799]
- EMBO shortterm fellowship
- Fondo de Investigacion Sanitaria Instituto de Salud Carlos III [FIS PI16/01605]
- Spanish Ministry of Science, Innovation and Universities [SAF2017-89109-P]
- Instituto de Salud Carlos III, Ministry of Health [PI16/00759]
- European Regional Development Fund-European Social Fund -FEDER-FSE
- UK Biotechnology and Biological Sciences Research Council [BBS/E/B/000C0426]
- Medical Research Council [MR/S000437/1]
- Grupo DISA [OA18/017]
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In this study, single-cell omics analyses were performed in CVID-discordant monozygotic twins, revealing epigenetic and transcriptional alterations associated with activation in memory B cells. These findings provide valuable insights into the diagnosis and treatment of CVID patients.
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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