Academic Journal
T-cell and monocyte DNA methylation and Wnt dysregulation in common variable immunodeficiency: an exploratory study.
| Τίτλος: | T-cell and monocyte DNA methylation and Wnt dysregulation in common variable immunodeficiency: an exploratory study. |
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| Συγγραφείς: | Myhre V; Research Institute of Internal Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Yang M; Department of Microbiology, Oslo University Hospital, Oslo, Norway.; Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway., Kaarbø M; Department of Microbiology, Oslo University Hospital, Oslo, Norway., Fraz MSA; Research Institute of Internal Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway., Michelsen AE; Research Institute of Internal Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Fevang B; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway., Aukrust P; Research Institute of Internal Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway., Ueland T; Research Institute of Internal Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Faculty of Health Sciences, K.G. Jebsen Centre for Thrombosis Research (TREC), University of Tromsø, Tromsø, Norway., Bjørås M; Department of Microbiology, Oslo University Hospital, Oslo, Norway.; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Norwegian University of Science and Technology, Trondheim, Norway.; Department of Microbiology, University of Oslo, Oslo, Norway., Jørgensen SF; Research Institute of Internal Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway.; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway. |
| Πηγή: | Frontiers in immunology [Front Immunol] 2026 Oct 01; Vol. 17, pp. 1931297. Date of Electronic Publication: 2026 Oct 01 (Print Publication: 2026). |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| Ιατρικοί όροι (MeSH): | Common Variable Immunodeficiency*/immunology , Common Variable Immunodeficiency*/genetics , Common Variable Immunodeficiency*/metabolism , T-Lymphocytes*/immunology , T-Lymphocytes*/metabolism , Monocytes*/immunology , Monocytes*/metabolism , Wnt Signaling Pathway*/genetics , Wnt Signaling Pathway*/immunology , DNA Methylation*, Humans ; Female ; Male ; Adult ; Epigenesis, Genetic ; Middle Aged ; CpG Islands |
| Περίληψη: | Background: Many patients with common variable immunodeficiency (CVID) develop inflammatory/autoimmune complications associated with T-cell and monocyte dysregulation which may involve epigenetic modifications. Objective: To characterize genome-wide CpG methylation in CD3+ T-cells and CD14+ monocytes in CVID and relate epigenetic alterations to gene expression and circulating proteins. Methods: Whole-genome bisulphite sequencing was performed on purified CD3+ T-cells and CD14+ monocytes from three CVID patients with inflammatory complications and three healthy controls per cell type. Differentially methylated cytosines were identified and analysed by pathway over-representation. Selected pathway-related proteins were measured in plasma from 60 CVID patients and 30 controls and evaluated in three public CVID transcriptomic datasets. Results: In this small discovery cohort, CVID was associated with widespread, cell type-specific methylation differences in T-cells and monocytes. T-cells showed a predominance of hypomethylated cytosines and regions, whereas monocytes displayed a more mixed pattern with roughly balanced hypo- and hypermethylation at individual sites. In T-cells, pathway analysis identified Wnt signalling, T-cell differentiation and actin organisation among the top differentially methylated processes. As Wnt signalling is underexplored in CVID and key Wnt modulators are measurable in plasma, we measured Wnt-related proteins in a larger CVID cohort and controls. In plasma, the Wnt antagonists DKK1 and DKK3 were reduced and Wnt agonist RSPO3 increased in CVID. Analyses of three public CVID transcriptomic datasets showed differential expression of Wnt-related genes. Monocyte pathway signals, mainly related to cell adhesion and actin organisation, were more heterogeneous and should be regarded as exploratory given the very small discovery cohort and the inclusion of a patient with a TNFAIP3 variant. Conclusion: In this explorative study we found that CVID is associated with extensive, cell type-specific epigenetic remodelling, particularly in T cells. Wnt signalling emerges as a recurrently altered pathway across DNA methylation, circulating proteins and gene expression, supporting Wnt-related mechanisms as a potential contributor to CVID immunopathology that should be further explored. (Copyright © 2026 Myhre, Yang, Kaarbø, Fraz, Michelsen, Fevang, Aukrust, Ueland, Bjørås and Jørgensen.) |
| Competing Interests: | The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors BF, PA declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. |
| Contributed Indexing: | Keywords: CVID - common variable immunodeficiency; CpG methylation;; T cells; Wnt signaling; autoimmunity; epigenetic; inflammation; monocytes |
| Entry Date(s): | Date Created: 20261017 Date Completed: 20261017 Latest Revision: 20261017 |
| Update Code: | 20261018 |
| PubMed Central ID: | PMC13668603 |
| DOI: | 10.3389/fimmu.2026.1931297 |
| PMID: | 42889152 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2026.1931297 |