Defective glycosylation and multisystem abnormalities characterize the primary immunodeficiency XMEN disease
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Le résumé fourni par la source
X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia (XMEN) disease are caused by deficiency of the magnesium transporter 1 (MAGT1) gene. We studied 23 patients with XMEN, 8 of whom were EBV naive. We observed lymphadenopathy (LAD), cytopenias, liver disease, cavum septum pellucidum (CSP), and increased CD4-CD8-B220-TCRαβ+ T cells (αβDNTs), in addition to the previously described features of an inverted CD4/CD8 ratio, CD4+ T lymphocytopenia, increased B cells, dysgammaglobulinemia, and decreased expression of the natural killer group 2, member D (NKG2D) receptor. EBV-associated B cell malignancies occurred frequently in EBV-infected patients. We studied patients with XMEN and patients with autoimmune lymphoproliferative syndrome (ALPS) by deep immunophenotyping (32 immune markers) using time-of-flight mass cytometry (CyTOF). Our analysis revealed that the abundance of 2 populations of naive B cells (CD20+CD27-CD22+IgM+HLA-DR+CXCR5+CXCR4++CD10+CD38+ and CD20+CD27-CD22+IgM+HLA-DR+CXCR5+CXCR4+CD10-CD38-) could differentially classify XMEN, ALPS, and healthy individuals. We also performed glycoproteomics analysis on T lymphocytes and show that XMEN disease is a congenital disorder of glycosylation that affects a restricted subset of glycoproteins. Transfection of MAGT1 mRNA enabled us to rescue proteins with defective glycosylation. Together, these data provide new clinical and pathophysiological foundations with important ramifications for the diagnosis and treatment of XMEN disease.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Defective glycosylation and multisystem abnormalities characterize the primary immunodeficiency XMEN disease
- Date Crossref
- 09/12/2019
- Éditeur
- American Society for Clinical Investigation
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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National Institute of Allergy and Infectious Diseases pays non établi dans la noticeStructure de recherche
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Max Planck Institute of Biochemistry Proteomics and Signal Transduction Group and Computational Systems Biochemistry pays non établi dans la noticeStructure de recherche
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Office of Extramural Research pays non établi dans la noticeOrganisme public
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National Institute of Neurological Disorders and Stroke Neuroimmunology Branch pays non établi dans la noticeStructure de recherche
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National Cancer Institute Center for Cancer Research pays non établi dans la noticeOrganisme public
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Center for Cancer Research pays non établi dans la noticeStructure de recherche
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Shenzhen Children's Hospital Department of Rheumatology and Immunology pays non établi dans la noticeÉtablissement de santé
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National Institute of Diabetes and Digestive and Kidney Diseases Liver Disease Branch pays non établi dans la noticeStructure de recherche
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Cancer Research And Biostatistics pays non établi dans la noticeOrganisation à but non lucratif
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National Human Genome Research Institute pays non établi dans la noticeStructure de recherche
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National Institutes of Health Clinical Center Radiology and Imaging Sciences pays non établi dans la noticeÉtablissement de santé
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Frederick National Laboratory for Cancer Research pays non établi dans la noticeStructure de recherche
National Institute of Allergy and Infectious Diseases, Proteomics and Signal Transduction Group and Computational Systems Biochemistry — Max Planck Institute of Biochemistry et Office of Extramural Research, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.