title: X-linked lymphoproliferative syndrome: a genetic condition typified by the triad of infection, immunodeficiency and lymphoma.
abstract: X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency characterized by the clinical triad of increased susceptibility to primary Epstein-Barr virus (EBV) infection, dysgammaglobulinaemia and lymphoma. Most cases are caused by germline mutations in the SH2D1A gene, which encodes the adaptor molecule Signalling Lymphocytic Activation Molecule (SLAM)-associated protein (SAP). Recently, a subset of patients with an XLP-like phenotype was found to carry mutations in XIAP, the gene encoding the X-linked inhibitor of apoptosis protein (XIAP). Studies of XLP patients and Sap-/- mice reveal that loss of SAP expression impairs immune cell activities, such as natural killer and CD8+ T cell cytotoxicity, T cell cytokine production, activation-induced cell death, germinal centre formation and natural killer T cell development. Efforts to dissect the diverse roles of SAP and XIAP are enhancing our understanding of immune cell biology and defining how genetic defects in these molecules predispose to EBV-specific as well as more general cellular and humoral immune dysfunction. These studies are also highlighting critical signalling pathways that might be amenable to pharmacological targeting to improve the treatment of XLP and other disorders associated with impaired antiviral and antitumour immunity.
authors.affiliation: Molecular Immunology Research Center, Department of Immunology, and School of Medicine, and Research Group for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Dr Qarib Street, Keshavarz Boulevard, Tehran, Iran. rezaei_nima@tums.ac.ir
authors.forename: Nima
authors.initials: N
authors.lastname: Rezaei
authors.forename: Elham
authors.initials: E
authors.lastname: Mahmoudi
authors.forename: Asghar
authors.initials: A
authors.lastname: Aghamohammadi
authors.forename: Rupali
authors.initials: R
authors.lastname: Das
authors.forename: Kim E
authors.initials: KE
authors.lastname: Nichols
mesh_terms: D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000235:genetics; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000235:genetics*; D008232:Lymphoproliferative Disorders / Q000150:complications / Q000235:genetics*; D009894:Opportunistic Infections / Q000150:complications / Q000235:genetics*; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein