Defective glycosylation and multisystem abnormalities characterize the primary immunodeficiency XMEN disease

Ravell, Juan C; Matsuda-Lennikov, Mami; Chauvin, Samuel D.; Zou, Juan; Biancalana, Matthew; Deeb, Sally J.; Price, Susan; Su, Helen C.; Notarangelo, Giulia; Jiang, Ping; Morawski, Aaron; Kanellopoulou, Chrysi; Binder, Kyle W.; Mukherjee, Ratnadeep; Anibal, James; Sellers, Brian; Zheng, Lixin; He, Tao; George, Alex; Pittaluga, Stefania; Powers, Astin S.; Kleiner, David E.; Kapuria, Devika; Ghany, Marc G.; Hunsberger, Sally; Cohen, Jeffrey I.; Uzel, Gülbû; Bergerson, Jenna; Wolfe, Lynne A.; Toro, Camilo; Gahl, William A.; Folio, Les; Matthews, Helen; Angelus, Pam; Chinn, Iván K.; Orange, Jordan S.; Trujillo-Vargas, Claudia M.; Franco, José Luis; Orrego-Arango, Julio; Gutierrez-Hincapié, Sebastian; Patel, Niraj; Raymond, Kimiyo; Patıroğlu, Türkan; Ünal, Ekrem; Karakükçü, Musa; Day, Alexandre G. R.; Mehta, Pankaj; Masutani, Evan; Ravin, Suk See De; Malech, Harry L.; Altan‐Bonnet, Grégoire; Rao, V. Koneti; Mann, Matthias; Lenardo, Michael J.

doi:10.1172/jci131116

Cited by 83 publications

(132 citation statements)

References 48 publications

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“…The classical example is severe combined immunodeficiency (SCID) with defects in T cells, B cells, and NK cells caused by defects in IL2RG, RAG1/2, ADA, JAK3, and IL7R genes, in which an increased risk of disseminated VZV infection has been well-recognized for many years (Arvin et al 2010 ; Carter-Timofte et al 2018b ; Fischer et al 2015 ; Zerboni et al 2014 ). Other combined PIDs mainly affecting T cells, NK cells, and to a lesser extent B cells, including CORONIN1A (Yee et al 2016 ), Wiskott Aldrich syndrome (Albert et al 2011 ), CARMIL2 (Schober et al 2017 ), MAGT1 (Ravell et al 2020 ), STK4 (Abdollahpour et al 2012 ), and CXCR4 (Heusinkveld et al 2017 ) deficiencies, have also been associated with recurrent zoster and/or persistent skin infection (Al-Herz and Essa 2019 ). The central role exerted by T cells in anti-VZV immunity is further demonstrated by the occurrence of severe varicella, pneumonia, or chronic VZV infection described in conditions involving the T cell surface molecules CD27 (Alkhairy et al 2015 ) and CD70 (Abolhassani et al 2017 ) as well STIM1 (Picard et al 2009 ).…”

Section: Host Factors That Determine Susceptibility To Vzv-associatedmentioning

confidence: 99%

“…infection Fischer et al ( 2015 ) CORO1A T and B cells Diss. infection, pneumonitis, meningitis Yee et al ( 2016 ) WAS All leukocytes Severe recurrent zoster Albert et al ( 2011 ) CARMIL2 T and B cell Recurrent varicella Schober et al ( 2017 ) MAGT1 T and NK cells Severe varicella, recurrent zoster Ravell et al ( 2020 ) STK4 T and B cells Recurrent severe zoster Abdollahpour et al ( 2012 ) CXCR4 T and B cells, neutrophils Recurrent zoster Heusinkveld et al ( 2017 ) CD27 T cells Severe varicella Alkhairy et al ( 2015 ) CD70 T cells Severe varicella Abolhassani et al ( 2017 ) STIM1 T cells Severe varicella, cellulitis Picard et al ( 2009 ) POL D1 T cells Severe recurrent varicella, encephalitis Cui et al ( 2020 ) STAT5B T and NK cells Hemorrhagic varicella, zoster, keratitis Bezrodnik et al ( 2015 ) DOCK2 T and NK cells Hemorrhagic varicella, pneumonitis Dobbs et al ( 2015 ) DOCK8 T, B, and NK cells Diss. VZV, CNS vasculopathy Zhang et al ( 2009 ); Sabry et al ( 2014 ) GATA2 Monocytes, NK, B cells Diss.…”

Section: Host Factors That Determine Susceptibility To Vzv-associatedmentioning

confidence: 99%

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Determinants of neurological syndromes caused by varicella zoster virus (VZV)

Kennedy

Mogensen

2020

J. Neurovirol.

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Varicella zoster virus (VZV) is a pathogenic human herpes virus which causes varicella as a primary infection, following which it becomes latent in peripheral autonomic, sensory, and cranial nerve ganglionic neurons from where it may reactivate after decades to cause herpes zoster. VZV reactivation may also cause a wide spectrum of neurological syndromes, in particular, acute encephalitis and vasculopathy. While there is potentially a large number of coding viral mutations that might predispose certain individuals to VZV infections, in practice, a variety of host factors are the main determinants of VZV infection, both disseminated and specifically affecting the nervous system. Host factors include increasing age with diminished cell-mediated immunity to VZV, several primary immunodeficiency syndromes, secondary immunodeficiency syndromes, and drug-induced immunosuppression. In some cases, the molecular immunological basis underlying the increased risk of VZV infections has been defined, in particular, the role of POL III mutations, but in other cases, the mechanisms have yet to be determined. The role of immunization in immunosuppressed individuals as well as its possible efficacy in preventing both generalized and CNS-specific infections will require further investigation to clarify in such patients.

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Section: Host Factors That Determine Susceptibility To Vzv-associatedmentioning

confidence: 99%

Section: Host Factors That Determine Susceptibility To Vzv-associatedmentioning

confidence: 99%

Determinants of neurological syndromes caused by varicella zoster virus (VZV)

Kennedy

Mogensen

2020

J. Neurovirol.

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“…One of the most relevant studies about the relationship between lymphocytes and Mg 2+ was described in the XMEN syndrome (X-linked immunodeficiency Mg 2+ defect, Epstein–Barr virus infection, and neoplasia), which was first described as Magt1 loss affecting intracellular Mg 2+ homeostasis and leading to defective T-cell immune responses and uncontrolled EBV infection with increased susceptibility to EBV + lymphoma [ 168 ]. This syndrome is a rare primary immunodeficiency caused by hemizygous loss-of-function mutations in the X-linked MagT1 gene in males [ 169 ]. Magt1 was initially recognized as an Mg 2+ transporter, and early studies placed it as a plasma membrane protein; however, more recent data also postulated that Magt1 is localized in the endoplasmic reticulum and is a subunit of the oligosaccharyltransferase (OST) complex and more specifically of the STT3B complex [ 170 ].…”

Section: The Role Of Mg 2+ In Hematopoiesismentioning

confidence: 99%

A Review of the Action of Magnesium on Several Processes Involved in the Modulation of Hematopoiesis

Lima

Fock

2020

IJMS

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Magnesium (Mg2+) is an essential mineral for the functioning and maintenance of the body. Disturbances in Mg2+ intracellular homeostasis result in cell-membrane modification, an increase in oxidative stress, alteration in the proliferation mechanism, differentiation, and apoptosis. Mg2+ deficiency often results in inflammation, with activation of inflammatory pathways and increased production of proinflammatory cytokines by immune cells. Immune cells and others that make up the blood system are from hematopoietic tissue in the bone marrow. The hematopoietic tissue is a tissue with high indices of renovation, and Mg2+ has a pivotal role in the cell replication process, as well as DNA and RNA synthesis. However, the impact of the intra- and extracellular disturbance of Mg2+ homeostasis on the hematopoietic tissue is little explored. This review deals specifically with the physiological requirements of Mg2+ on hematopoiesis, showing various studies related to the physiological requirements and the effects of deficiency or excess of this mineral on the hematopoiesis regulation, as well as on the specific process of erythropoiesis, granulopoiesis, lymphopoiesis, and thrombopoiesis. The literature selected includes studies in vitro, in animal models, and in humans, giving details about the impact that alterations of Mg2+ homeostasis can have on hematopoietic cells and hematopoietic tissue.

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“…Recently, it has been shown that MAGT1-dependent glycosylation is sensitive to Mg 2+ levels, and that reduced Mg 2+ impairs immune cell function via the loss of specific glycoproteins, i.e., CD28 [80]. Most XMEN patients develop mild to moderate thrombocytopenia [112,113], although a detailed description of megakaryocyte and platelet functions have not been reported yet. Magt -/y mice have normal platelet count and size, although an altered ploidy of megakaryocytes was detected; but this mild defect did not influence platelet production [114].…”

Section: Platelets In Congenital Disorders Of N-glycosylationmentioning

confidence: 99%

Platelets and Defective N-Glycosylation

Mammadova‐Bach

Jaeken

Gudermann

et al. 2020

IJMS

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N-glycans are covalently linked to an asparagine residue in a simple acceptor sequence of proteins, called a sequon. This modification is important for protein folding, enhancing thermodynamic stability, and decreasing abnormal protein aggregation within the endoplasmic reticulum (ER), for the lifetime and for the subcellular localization of proteins besides other functions. Hypoglycosylation is the hallmark of a group of rare genetic diseases called congenital disorders of glycosylation (CDG). These diseases are due to defects in glycan synthesis, processing, and attachment to proteins and lipids, thereby modifying signaling functions and metabolic pathways. Defects in N-glycosylation and O-glycosylation constitute the largest CDG groups. Clotting and anticlotting factor defects as well as a tendency to thrombosis or bleeding have been described in CDG patients. However, N-glycosylation of platelet proteins has been poorly investigated in CDG. In this review, we highlight normal and deficient N-glycosylation of platelet-derived molecules and discuss the involvement of platelets in the congenital disorders of N-glycosylation.

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Defective glycosylation and multisystem abnormalities characterize the primary immunodeficiency XMEN disease

Cited by 83 publications

References 48 publications

Determinants of neurological syndromes caused by varicella zoster virus (VZV)

Determinants of neurological syndromes caused by varicella zoster virus (VZV)

A Review of the Action of Magnesium on Several Processes Involved in the Modulation of Hematopoiesis

Platelets and Defective N-Glycosylation

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