title: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia disease: a combined immune deficiency with magnesium defect.
abstract: OBJECTIVE
  To describe the role of the magnesium transporter 1 (MAGT1) in the pathogenesis of 'X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia' (XMEN) disease and its clinical implications.
  
  
  RESULTS
  The magnesium transporter protein MAGT1 participates in the intracellular magnesium ion (Mg) homeostasis and facilitates a transient Mg influx induced by the activation of the T-cell receptor. Loss-of-function mutations in MAGT1 cause an immunodeficiency named 'XMEN syndrome', characterized by CD4 lymphopenia, chronic EBV infection, and EBV-related lymphoproliferative disorders. Patients with XMEN disease have impaired T-cell activation and decreased cytolytic function of natural killer (NK) and CD8 T cells because of decreased expression of the NK stimulatory receptor 'natural-killer group 2, member D' (NKG2D). Patients may have defective specific antibody responses secondary to T cell dysfunction, but B cells have not been shown to be directly affected by mutations in MAGT1.
  
  
  CONCLUSIONS
  XMEN disease has revealed a novel role for free intracellular magnesium in the immune system. Further understanding of the MAGT1 signaling pathway may lead to new diagnostic and therapeutic approaches.
authors.affiliation: aMolecular Development of the Immune System Section, Lymphocyte Molecular Genetics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health bNIAID Clinical Genomics Program, Bethesda, Maryland, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Ravell
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chaigne-Delalande
authors.forename: Michael
authors.initials: M
authors.lastname: Lenardo
mesh_terms: D027682:Cation Transport Proteins; D002648:Child; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D006801:Humans; D008275:Magnesium Deficiency / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D008297:Male; D009369:Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D013577:Syndrome; D053632:X-Linked Combined Immunodeficiency Diseases / Q000150:complications* / Q000175:diagnosis / Q000628:therapy
chemical_list: D027682:Cation Transport Proteins; C509698:MagT1 protein, human