Journal of Clinical Immunology

, Volume 35, Issue 4, pp 331–338

X-linked Inhibitor of Apoptosis Protein Deficiency: More than an X-linked Lymphoproliferative Syndrome

CME Review

DOI: 10.1007/s10875-015-0141-9

Cite this article as:
Aguilar, C. & Latour, S. J Clin Immunol (2015) 35: 331. doi:10.1007/s10875-015-0141-9


X-linked inhibitor of apoptosis (XIAP) deficiency (also known as X-linked lymphoproliferative syndrome type 2, XLP-2) is a rare primary immunodeficiency. Since the disease was first described in 2006, more than 70 patients suffering from XIAP-deficiency have been reported, thus extending the clinical presentations of the disease. The main clinical features of XLP-2 are (i) elevated susceptibility to hemophagocytic lymphohistiocytosis (HLH, frequently in response to infection with Epstein-Barr virus (EBV)), (ii) recurrent splenomegaly and (iii) inflammatory bowel disease (IBD) with the characteristics of Crohn’s disease. XIAP deficiency is now considered to be one of the genetic causes of IBD in infancy. Although XIAP is an anti-apoptotic molecule, it is also involved in many other pathways, including the regulation of innate immunity and inflammation. XIAP is required for signaling through the Nod-like receptors NOD1 and 2, which are intracellular sensors of bacterial infection. XIAP-deficient T cells (including innate natural killer T cells and mucosal-associated invariant T cells) are overly sensitive to apoptosis. NOD2 function is impaired in XIAP-deficient monocytes. However, the physiopathological mechanisms underlying the clinical phenotypes in XIAP deficiency, notably the HLH and the EBV susceptibility, are not well understood. Here, we review the clinical aspects, molecular etiology and physiopathology of XIAP deficiency.


X-linked lymphoproliferative syndrome hemophagocytic lymphohistiocytosis inflammatory bowel disease crohn’s disease susceptibility to EBV infection 

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, INSERM UMR 1163Descartes-Sorbonne Paris Cité University of Paris and Institut ImagineParisFrance
  2. 2.Laboratory of Lymphocyte Activation and Susceptibility to EBV InfectionImagine – Institut des maladies génétiques - INSERM UMR 1163ParisFrance