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X‐linked lymphoproliferative syndrome: a genetic condition typified by the triad of infection, immunodeficiency and lymphoma
Author(s) -
Rezaei Nima,
Mahmoudi Elham,
Aghamohammadi Asghar,
Das Rupali,
Nichols Kim E.
Publication year - 2011
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2010.08442.x
Subject(s) - lymphoma , triad (sociology) , medicine , human immunodeficiency virus (hiv) , immunology , immunodeficiency , virology , immune system , psychology , psychoanalysis
Summary 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.