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  Defective glycosylation and multisystem abnormalities characterize the primary immunodeficiency XMEN disease

Ravell, J. C., Matsuda-Lennikov, M., Chauvin, S. D., Zou, J., Biancalana, M., Deeb, S. J., et al. (2020). Defective glycosylation and multisystem abnormalities characterize the primary immunodeficiency XMEN disease. JOURNAL OF CLINICAL INVESTIGATION, 130(1), 507-522. doi:10.1172/JCI131116.

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 Creators:
Ravell, Juan C.1, Author
Matsuda-Lennikov, Mami1, Author
Chauvin, Samuel D.1, Author
Zou, Juan1, Author
Biancalana, Matthew1, Author
Deeb, Sally J.2, Author           
Price, Susan1, Author
Su, Helen C.1, Author
Notarangelo, Giulia1, Author
Jiang, Ping1, Author
Morawski, Aaron1, Author
Kanellopoulou, Chrysi1, Author
Binder, Kyle1, Author
Mukherjee, Ratnadeep1, Author
Anibal, James T.1, Author
Sellers, Brian1, Author
Zheng, Lixin1, Author
He, Tingyan1, Author
George, Alex B.1, Author
Pittaluga, Stefania1, Author
Powers, Astin1, AuthorKleiner, David E.1, AuthorKapuria, Devika1, AuthorGhany, Marc1, AuthorHunsberger, Sally1, AuthorCohen, Jeffrey I.1, AuthorUzel, Gulbu1, AuthorBergerson, Jenna1, AuthorWolfe, Lynne1, AuthorToro, Camilo1, AuthorGahl, William1, AuthorFolio, Les R.1, AuthorMatthews, Helen1, AuthorAngelus, Pam1, AuthorChinn, Ivan K.1, AuthorOrange, Jordan S.1, AuthorTrujillo-Vargas, Claudia M.1, AuthorFranco, Jose Luis1, AuthorOrrego-Arango, Julio1, AuthorGutierrez-Hincapie, Sebastian1, AuthorPatel, Niraj Chandrakant1, AuthorRaymond, Kimiyo1, AuthorPatiroglu, Turkan1, AuthorUnal, Ekrem1, AuthorKarakukcu, Musa1, AuthorDay, Alexandre G. R.1, AuthorMehta, Pankaj1, AuthorMasutani, Evan1, AuthorDe Ravin, Suk S.1, AuthorMalech, Harry L.1, AuthorAltan-Bonnet, Gregoire1, AuthorRao, V. Koneti1, AuthorMann, Matthias2, Author           Lenardo, Michael J.1, Author more..
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: CONGENITAL DISORDERS; LYMPHOPROLIFERATIVE SYNDROME; T-CELLS; OXIDOREDUCTASE ACTIVITY; N-GLYCOSYLATION; MASS CYTOMETRY; MUTATIONS; MAGT1; GENE; INFECTION
 Abstract: 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-TCR alpha beta(+) T cells (alpha beta DNTs), 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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Language(s): eng - English
 Dates: 2020
 Publication Status: Published in print
 Pages: 16
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000505205000048
DOI: 10.1172/JCI131116
 Degree: -

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Title: JOURNAL OF CLINICAL INVESTIGATION
Source Genre: Journal
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Publ. Info: 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA : AMER SOC CLINICAL INVESTIGATION INC
Pages: - Volume / Issue: 130 (1) Sequence Number: - Start / End Page: 507 - 522 Identifier: ISSN: 0021-9738