X-linked immunodeficiency with magnesium defect, Epstein–Barr virus infection, and neoplasia disease

Ravell, Juan C; Chaigne-Delalande, Benjamin; Lenardo, Michael J.

doi:10.1097/mop.0000000000000156

Cited by 58 publications

(35 citation statements)

References 46 publications

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“…In 91 patients with X‐linked lymphoproliferative syndrome type 1, a disorder associated with aggressive HLH at primary EBV infection, 24% had had a malignant lymphoproliferative disorder, usually B‐lineage NHL (Booth et al , ). EBV‐susceptibility and a propensity to lymphoma has been found in primary immunodeficiences caused by mutations in magnesium transporter 1 ( MAGT1 , resulting in X‐linked immunodeficiency with Magnesium defect, EBV infection and Neoplasia, XMEN) and interleukin‐2‐inducible T‐cell kinase ( ITK ) (Ghosh et al , ; Ravell et al , ). In the latter, occasional occurrence of at least partial HLH has also been reported.…”

Section: Discussionmentioning

confidence: 99%

Malignancy‐associated haemophagocytic lymphohistiocytosis in children and adolescents

et al. 2015

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SummaryHaemophagocytic lymphohistiocytosis (HLH) in the context of malignancy is mainly considered a challenge of adult haematology. While this association is also observed in children, little is known regarding inciting factors, appropriate treatment and prognosis. We retrospectively analysed 29 paediatric and adolescent patients for presenting features, type of neoplasm or preceding chemotherapy, treatment and outcome. Haemophagocytic lymphohistiocytosis was considered triggered by the malignancy (M-HLH) in 21 patients, most of whom had T-(n = 12) or B-cell neoplasms (n = 7), with Epstein-Barr virus as a co-trigger in five patients. In eight patients, HLH occurred during chemotherapy (Ch-HLH) for malignancy, mainly acute leukaemias (n = 7); an infectious trigger was found in seven. In Mand Ch-HLH, median overall survival was 1Á2 and 0Á9 years, and the 6 month survival rates were 67% and 63%, respectively. Seven of 11 deceased M-HLH patients exhibited active malignancy and HLH at the time of death, while only two out of five deceased Ch-HLH patients had evidence of active HLH. To overcome HLH, malignancy-and HLH-directed treatments were administered in the M-HLH cohort; however, it was not possible to determine superiority of one approach over the other. For Ch-HLH, treatment ranged from postponement of chemotherapy to the use of etoposide-containing regimens.

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Section: Discussionmentioning

confidence: 99%

Malignancy‐associated haemophagocytic lymphohistiocytosis in children and adolescents

et al. 2015

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“…To date, eight patients have been described with an age at diagnosis of 3-58 years (Ravell et al, 2014;Dhalla et al, 2015). Patients also develop other viral infections, such as Molluscum, herpes simplex virus and varicella zoster virus (VZV), and recurrent sinopulmonary infections (Ravell et al, 2014). A decreased CD4:CD8 ratio is a consistent finding with abnormal T cell receptor (TCR) signalling, but significant humoral defects have not been described (Li et al, 2014).…”

Section: Cd27 Deficiencymentioning

confidence: 99%

“…It is characterised by chronic EBV infection with high viral loads, and increased susceptibility to lymphoma and LPD. To date, eight patients have been described with an age at diagnosis of 3-58 years (Ravell et al, 2014;Dhalla et al, 2015). None have developed HLH or other overt features of immune dysregulation, unlike the other X-linked lymphoproliferative disorders.…”

Section: Cd27 Deficiencymentioning

confidence: 99%

“…Due to abnormal magnesium flux in NK and T-cells, viral specific cytotoxic cells fail to sufficiently control EBV infection. Patients also develop other viral infections, such as Molluscum, herpes simplex virus and varicella zoster virus (VZV), and recurrent sinopulmonary infections (Ravell et al, 2014). Haematological malignancy is reported in all post-pubertal patients described, with many experiencing LPD early in life.…”

Section: Cd27 Deficiencymentioning

confidence: 99%

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Severe Epstein–Barr virus infection in primary immunodeficiency and the normal host

Worth

Houldcroft²,

Booth

2016

Br J Haematol

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Epstein-Barr virus (EBV) infection is ubiquitous in humans, but the majority of infections have an asymptomatic or self-limiting clinical course. Rarely, individuals may develop a pathological EBV infection with a variety of life threatening complications (including haemophagocytosis and malignancy) and others develop asymptomatic chronic EBV viraemia. Although an impaired ability to control EBV infection has long been recognised as a hallmark of severe T-cell immunodeficiency, the advent of next generation sequencing has identified a series of Primary Immunodeficiencies in which EBV-related pathology is the dominant feature. Chronic active EBV infection is defined as chronic EBV viraemia associated with systemic lymphoproliferative disease, in the absence of immunodeficiency. Descriptions of larger cohorts of patients with chronic active EBV in recent years have significantly advanced our understanding of this clinical syndrome. In this review we summarise the current understanding of the pathophysiology and natural history of these diseases and clinical syndromes, and discuss approaches to the investigation and treatment of severe or atypical EBV infection.

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“…MAGT1 (OMIM 300715) is located on human chromosome X, band Xq21.1 (base pairs 77,826,364 to 77,895,593 (GRCh38/hg38), and consists of 10 exons (69.4 kb). There are three protein coding isoforms of MAGT1 coding for 367 (isoform 201), 355 (isoform 004) and 134 (isoform 002) amino acids [19,20] (figure 1). Based on different transmembrane (TM) prediction methods, MAGT1 could contain four to five TM domains [10,11], but recent studies are more in agreement with the former model [21].…”

Section: Magt1 In Humansmentioning

confidence: 99%

The role of MAGT1 in genetic syndromes

Trapani¹,

Shomer

Rajcan‐Separovic

2015

Magnesium Research

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Disturbances in magnesium homeostasis, often linked to altered expression and/or function of magnesium channels, have been implicated in a plethora of diseases. This review focuses on magnesium transporter 1 (MAGT1), as recently described changes in this gene have further extended our understanding of the role of magnesium in human health and disease. The identification of genetic changes and their functional consequences in patients with immunodeficiency revealed that magnesium and MAGT1 are key molecular players for T cell-mediated immune responses. This led to the description of XMEN (X-linked immunodeficiency with magnesium defect, Epstein Barr Virus infection, and neoplasia) syndrome, for which Mg 2+ supplementation has been shown to be beneficial. Similarly, the identification of a copy-number variation (CNV) leading to dysfunctional MAGT1 in a family with atypical ATRX syndrome and skin abnormalities, suggested that the MAGT1 defect could be responsible for the cutaneous problems. On the other hand, recent genetic investigations question the previously proposed role for MAGT1 in intellectual disability. Understanding the molecular basis of the involvement of magnesium and its channels in human pathogenesis will improve opportunities for Mg 2+ therapies in the clinic.

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X-linked immunodeficiency with magnesium defect, Epstein–Barr virus infection, and neoplasia disease

Cited by 58 publications

References 46 publications

Malignancy‐associated haemophagocytic lymphohistiocytosis in children and adolescents

Malignancy‐associated haemophagocytic lymphohistiocytosis in children and adolescents

Severe Epstein–Barr virus infection in primary immunodeficiency and the normal host

The role of MAGT1 in genetic syndromes

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