{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T07:41:26Z","timestamp":1792136486860,"version":"4.4.0"},"reference-count":121,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T00:00:00Z","timestamp":1623888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>X-linked inhibitor of apoptosis (XIAP) deficiency is a rare inborn error of immunity first described in 2006. XIAP deficiency is characterised by immune dysregulation and a broad spectrum of clinical manifestations, including haemophagocytic lymphohistiocytosis (HLH), inflammatory bowel disease (IBD), hypogammaglobulinemia, susceptibility to infections, splenomegaly, cytopaenias, and other less common autoinflammatory phenomena. Since the first description of the disease, many XIAP deficient patients have been identified and our understanding of the disease has grown. Over 90 disease causing mutations have been described and more inflammatory disease manifestations, such as hepatitis, arthritis, and uveitis, are now well-recognised. Recently, following the introduction of reduced intensity conditioning (RIC), outcomes of allogeneic haematopoietic stem cell transplantation (HSCT), the only curative treatment option for XIAP deficiency, have improved. The pathophysiology of XIAP deficiency is not fully understood, however it is known that XIAP plays a role in both the innate and adaptive immune response and in immune regulation, most notably through modulation of tumour necrosis factor (TNF)-receptor signalling and regulation of NLRP3 inflammasome activity. In this review we will provide an up to date overview of both the clinical aspects and pathophysiology of XIAP deficiency.<\/jats:p>","DOI":"10.3389\/fped.2021.660520","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T04:22:46Z","timestamp":1623903766000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":86,"title":["Evolution of Our Understanding of XIAP Deficiency"],"prefix":"10.3389","volume":"9","author":[{"given":"Anne C. A.","family":"Mudde","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Booth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Marsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.semcdb.2015.01.015","article-title":"XIAP deficiency syndrome in humans","volume":"39","author":"Latour","year":"2015","journal-title":"Semin Cell Dev Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/nature05257","article-title":"XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome","volume":"444","author":"Rigaud","year":"2006","journal-title":"Nature."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1182\/blood-2010-01-256099","article-title":"XIAP deficiency: a unique primary immunodeficiency best classified as X-linked familial hemophagocytic lymphohistiocytosis and not as X-linked lymphoproliferative disease","volume":"116","author":"Marsh","year":"2010","journal-title":"Blood."},{"key":"B4","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.clim.2013.07.004","article-title":"X-linked inhibitor of apoptosis (XIAP) deficiency: the spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis","volume":"149","author":"Speckmann","year":"2013","journal-title":"Clin Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1002\/emmm.201303090","article-title":"Disease-causing mutations in the XIAP BIR2 domain impair NOD2-dependent immune signalling","volume":"5","author":"Damgaard","year":"2013","journal-title":"EMBO Mol Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1016\/j.celrep.2014.05.008","article-title":"XIAP restricts TNF- and RIP3-dependent cell death and inflammasome activation","volume":"7","author":"Yabal","year":"2014","journal-title":"Cell Rep."},{"key":"B7","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/379349a0","article-title":"Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes","volume":"379","author":"Liston","year":"1996","journal-title":"Nature."},{"key":"B8","doi-asserted-by":"publisher","first-page":"4974","DOI":"10.1073\/pnas.93.10.4974","article-title":"Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and\/or bind tumor necrosis factor receptor-associated factors","volume":"93","author":"Uren","year":"1996","journal-title":"Proc Natl Acad Sci USA."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2685","DOI":"10.1002\/j.1460-2075.1996.tb00629.x","article-title":"A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors","volume":"15","author":"Duckett","year":"1996","journal-title":"EMBO J."},{"key":"B10","doi-asserted-by":"publisher","first-page":"688","DOI":"10.3324\/haematol.2009.018010","article-title":"A novel XIAP mutation in a Japanese boy with recurrent pancytopenia and splenomegaly","volume":"95","author":"Zhao","year":"2010","journal-title":"Haematologica."},{"key":"B11","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1007\/s10875-011-9638-z","article-title":"Clinical and genetic characteristics of XIAP deficiency in Japan","volume":"32","author":"Yang","year":"2012","journal-title":"J Clin Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3398","DOI":"10.1182\/blood-2010-03-275909","article-title":"X-linked lymphoproliferative syndromes: brothers or distant cousins?","volume":"116","author":"Filipovich","year":"2010","journal-title":"Blood."},{"key":"B13","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1203\/00006450-199510000-00001","article-title":"X-linked lymphoproliferative disease: twenty-five years after the discovery","volume":"38","author":"Seemayer","year":"1995","journal-title":"Pediatr Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1182\/blood-2010-07-298372","article-title":"Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1\/SAP deficiency) versus type 2 (XLP-2\/XIAP deficiency)","volume":"117","author":"Pachlopnik Schmid","year":"2011","journal-title":"Blood."},{"key":"B15","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1182\/blood-2010-06-284935","article-title":"X-linked lymphoproliferative disease due to SAP\/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease","volume":"117","author":"Booth","year":"2011","journal-title":"Blood."},{"key":"B16","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s10875-015-0141-9","article-title":"X-linked inhibitor of apoptosis protein deficiency: more than an X-linked lymphoproliferative syndrome","volume":"35","author":"Aguilar","year":"2015","journal-title":"J Clin Immunol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1111\/cei.12427","article-title":"A mutation in X-linked inhibitor of apoptosis (G466X) leads to memory inflation of Epstein-Barr virus-specific T cells","volume":"178","author":"Lopez-Granados","year":"2014","journal-title":"Clin Exp Immunol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1038\/sj.embor.7400795","article-title":"Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family","volume":"7","author":"Eckelman","year":"2006","journal-title":"EMBO Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1016\/j.molmed.2014.09.006","article-title":"Inhibitors of apoptosis (IAPs) regulate intestinal immunity and inflammatory bowel disease (IBD) inflammation","volume":"20","author":"Pedersen","year":"2014","journal-title":"Trends Mol Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e101","DOI":"10.1097\/MPG.0000000000001536","article-title":"Monozygotic twin cases of XIAP deficiency syndrome","volume":"67","author":"Kim","year":"2018","journal-title":"J Pediatr Gastroenterol Nutr."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1016\/j.jaci.2014.04.031","article-title":"Characterization of Crohn disease in X-linked inhibitor of apoptosis-deficient male patients and female symptomatic carriers","volume":"134","author":"Aguilar","year":"2014","journal-title":"J Allergy Clin Immunol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1182\/blood-2011-01-328849","article-title":"Human X-linked variable immunodeficiency caused by a hypomorphic mutation in XIAP in association with a rare polymorphism in CD40LG","volume":"118","author":"Rigaud","year":"2011","journal-title":"Blood."},{"key":"B23","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1007\/s10875-015-0144-6","article-title":"A female patient with incomplete hemophagocytic lymphohistiocytosis caused by a heterozygous XIAP mutation associated with non-random X-chromosome inactivation skewed towards the wild-type XIAP allele","volume":"35","author":"Yang","year":"2015","journal-title":"J Clin Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1007\/s10875-015-0166-0","article-title":"Symptomatic males and female carriers in a large Caucasian kindred with XIAP deficiency","volume":"35","author":"Dziadzio","year":"2015","journal-title":"J Clin Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"5242","DOI":"10.1093\/emboj\/18.19.5242","article-title":"Cleavage of human inhibitor of apoptosis protein XIAP results in fragments with distinct specificities for caspases","volume":"18","author":"Deveraux","year":"1999","journal-title":"EMBO J."},{"key":"B26","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/sj.emboj.7600544","article-title":"XIAP inhibits caspase-3 and\u22127 using two binding sites: evolutionarily conserved mechanism of IAPs","volume":"24","author":"Scott","year":"2005","journal-title":"EMBO J."},{"key":"B27","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/S1097-2765(03)00054-6","article-title":"Mechanism of XIAP-mediated inhibition of caspase-9","volume":"11","author":"Shiozaki","year":"2003","journal-title":"Mol Cell."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1182\/blood-2014-03-564609","article-title":"Inability to resolve specific infection generates innate immunodeficiency syndrome in Xiap-\/- mice","volume":"124","author":"Hsieh","year":"2014","journal-title":"Blood."},{"key":"B29","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1038\/35085597","article-title":"TAK1 is a ubiquitin-dependent kinase of MKK and IKK","volume":"412","author":"Wang","year":"2001","journal-title":"Nature"},{"key":"B30","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/j.molcel.2007.05.006","article-title":"XIAP induces NF-kappaB activation via the BIR1\/TAB1 interaction and BIR1 dimerization","volume":"26","author":"Lu","year":"2007","journal-title":"Mol Cell"},{"key":"B31","doi-asserted-by":"publisher","first-page":"6015","DOI":"10.1073\/pnas.95.11.6015","article-title":"Selective activation of JNK1 is necessary for the anti-apoptotic activity of hILP","volume":"95","author":"Sanna","year":"","journal-title":"Proc Natl Acad Sci USA. (1"},{"key":"B32","doi-asserted-by":"publisher","first-page":"514","DOI":"10.4049\/jimmunol.179.1.514","article-title":"Nod1\/RICK and TLR signaling regulate chemokine and antimicrobial innate immune responses in mesothelial cells","volume":"179","author":"Park","year":"2007","journal-title":"J Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"36223","DOI":"10.1074\/jbc.M703079200","article-title":"NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection involves the stable polyubiquitination of Rip2","volume":"282","author":"Yang","year":"2007","journal-title":"J Biol Chem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1038\/ncb1789","article-title":"IAPs contain an evolutionarily conserved ubiquitin-binding domain that regulates NF-kappaB as well as cell survival and oncogenesis","volume":"10","author":"Gyrd-Hansen","year":"2008","journal-title":"Nat Cell Biol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/nrm1621","article-title":"IAPs, RINGs and ubiquitylation","volume":"6","author":"Vaux","year":"2005","journal-title":"Nat Rev Mol Cell Biol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1016\/j.molcel.2012.04.014","article-title":"The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity","volume":"46","author":"Damgaard","year":"2012","journal-title":"Mol Cell."},{"key":"B37","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1038\/40901","article-title":"X-linked IAP is a direct inhibitor of cell-death proteases","volume":"388","author":"Deveraux","year":"1997","journal-title":"Nature."},{"key":"B38","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/S0092-8674(01)00272-0","article-title":"Structural basis of caspase-7 inhibition by XIAP","volume":"104","author":"Chai","year":"2001","journal-title":"Cell."},{"key":"B39","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/S0092-8674(02)02075-5","article-title":"Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain","volume":"104","author":"Huang","year":"2001","journal-title":"Cell."},{"key":"B40","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/j.immuni.2009.04.011","article-title":"Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for innate immunity signaling by the pattern recognition receptors NOD1 and NOD2","volume":"30","author":"Bertrand","year":"2009","journal-title":"Immunity."},{"key":"B41","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/nri3565","article-title":"NOD proteins: regulators of inflammation in health and disease","volume":"14","author":"Philpott","year":"2014","journal-title":"Nat Rev Immunol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s00281-007-0083-2","article-title":"The Nodosome: Nod1 and Nod2 control bacterial infections and inflammation","volume":"29","author":"Tattoli","year":"2007","journal-title":"Semin Immunopathol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/sj.emboj.7601962","article-title":"A critical role of RICK\/RIP2 polyubiquitination in Nod-induced NF-kappaB activation","volume":"27","author":"Hasegawa","year":"2008","journal-title":"EMBO J."},{"key":"B44","doi-asserted-by":"publisher","first-page":"327","DOI":"10.3389\/fimmu.2014.00327","article-title":"NOD-Like Receptors: Master Regulators of Inflammation and Cancer","volume":"5","author":"Saxena","year":"2014","journal-title":"Front Immunol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1507\/endocrj.EJ12-0148","article-title":"Linear ubiquitination: a novel NF-kappaB regulatory mechanism for inflammatory and immune responses by the LUBAC ubiquitin ligase complex","volume":"59","author":"Tokunaga","year":"2012","journal-title":"Endocr J."},{"key":"B46","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.molcel.2014.10.021","article-title":"RIP3 induces apoptosis independent of pronecrotic kinase activity","volume":"56","author":"Mandal","year":"2014","journal-title":"Mol Cell."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1126\/science.1249361","article-title":"Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis","volume":"343","author":"Newton","year":"2014","journal-title":"Science."},{"key":"B48","doi-asserted-by":"publisher","first-page":"6282","DOI":"10.1038\/ncomms7282","article-title":"RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL","volume":"6","author":"Lawlor","year":"2015","journal-title":"Nat Commun."},{"key":"B49","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.celrep.2017.06.073","article-title":"XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1beta activation and cell death as a consequence of TLR-MyD88-induced cIAP1-TRAF2 degradation","volume":"20","author":"Lawlor","year":"2017","journal-title":"Cell Rep."},{"key":"B50","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1038\/s41419-019-1938-x","article-title":"TNFR2 induced priming of the inflammasome leads to a RIPK1-dependent cell death in the absence of XIAP","volume":"10","author":"Knop","year":"2019","journal-title":"Cell Death Dis."},{"key":"B51","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1097\/GIM.0b013e3182088158","article-title":"Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease","volume":"13","author":"Worthey","year":"2011","journal-title":"Genet Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1182\/blood-2012-09-456095","article-title":"Human iNKT and MAIT cells exhibit a PLZF-dependent proapoptotic propensity that is counterbalanced by XIAP","volume":"121","author":"Gerart","year":"2013","journal-title":"Blood."},{"key":"B53","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1038\/ni.2369","article-title":"C-type lectin receptors orchestrate antifungal immunity","volume":"13","author":"Hardison","year":"2012","journal-title":"Nat Immunol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1038\/emboj.2012.18","article-title":"IAPs limit activation of RIP kinases by TNF receptor 1 during development","volume":"31","author":"Moulin","year":"2012","journal-title":"EMBO J."},{"key":"B55","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/nrm3737","article-title":"Regulated necrosis: the expanding network of non-apoptotic cell death pathways","volume":"15","author":"Vanden Berghe","year":"2014","journal-title":"Nat Rev Mol Cell Biol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.immuni.2012.01.012","article-title":"Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation","volume":"36","author":"Vince","year":"2012","journal-title":"Immunity."},{"key":"B57","doi-asserted-by":"publisher","first-page":"2562","DOI":"10.1182\/blood-2013-06-510743","article-title":"cIAPs and XIAP regulate myelopoiesis through cytokine production in an RIPK1- and RIPK3-dependent manner","volume":"123","author":"Wong","year":"2014","journal-title":"Blood."},{"key":"B58","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1007\/s11882-010-0160-9","article-title":"Cryopyrin-associated periodic syndrome: an update on diagnosis and treatment response","volume":"11","author":"Yu","year":"2011","journal-title":"Curr Allergy Asthma Rep."},{"key":"B59","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.1136\/annrheumdis-2013-204991","article-title":"Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever Registry","volume":"74","author":"Levy","year":"2015","journal-title":"Ann Rheum Dis."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1136\/gutjnl-2015-310382","article-title":"Impaired antibacterial autophagy links granulomatous intestinal inflammation in Niemann-Pick disease type C1 and XIAP deficiency with NOD2 variants in Crohn's disease","volume":"66","author":"Schwerd","year":"2017","journal-title":"Gut."},{"key":"B61","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1038\/s41419-018-0508-y","article-title":"Inhibitor of apoptosis proteins are required for effective fusion of autophagosomes with lysosomes","volume":"9","author":"Gradzka","year":"2018","journal-title":"Cell Death Dis."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1038\/ng.3066","article-title":"Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation","volume":"46","author":"Romberg","year":"2014","journal-title":"Nat Genet"},{"key":"B63","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/35079107","article-title":"Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease","volume":"411","author":"Hugot","year":"2001","journal-title":"Nature"},{"key":"B64","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1038\/35079114","article-title":"A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease","volume":"411","author":"Ogura","year":"2001","journal-title":"Nature"},{"key":"B65","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1111\/imr.12193","article-title":"Cellular and molecular mechanisms underlying NOD2 risk-associated polymorphisms in Crohn's disease","volume":"260","author":"Strober","year":"2014","journal-title":"Immunol Rev"},{"key":"B66","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/S0140-6736(06)68265-2","article-title":"Defective acute inflammation in Crohn's disease: a clinical investigation","volume":"367","author":"Marks","year":"2006","journal-title":"Lancet"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1084\/jem.20091233","article-title":"Disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease","volume":"206","author":"Smith","year":"2009","journal-title":"J Exp Med"},{"key":"B68","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1084\/jem.20091683","article-title":"Revisiting Crohn's disease as a primary immunodeficiency of macrophages","volume":"206","author":"Casanova","year":"2009","journal-title":"J Exp Med"},{"key":"B69","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1126\/science.1104911","article-title":"Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract","volume":"307","author":"Kobayashi","year":"2005","journal-title":"Science"},{"key":"B70","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/S0016-5085(03)00661-9","article-title":"Crohn's disease and the NOD2 gene: a role for paneth cells","volume":"125","author":"Lala","year":"2003","journal-title":"Gastroenterology"},{"key":"B71","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1136\/gut.52.11.1591","article-title":"Expression of NOD2 in Paneth cells: a possible link to Crohn's ileitis","volume":"52","author":"Ogura","year":"2003","journal-title":"Gut"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1136\/gut.2003.032805","article-title":"NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression","volume":"53","author":"Wehkamp","year":"2004","journal-title":"Gut"},{"key":"B73","doi-asserted-by":"publisher","first-page":"2052","DOI":"10.1002\/eji.200425229","article-title":"NOD2 mediates anti-inflammatory signals induced by TLR2 ligands: implications for Crohn's disease","volume":"34","author":"Netea","year":"2004","journal-title":"Eur J Immunol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1111\/j.1749-6632.2011.06339.x","article-title":"IL-10 and IL-10 receptor defects in humans","volume":"1246","author":"Glocker","year":"2011","journal-title":"Ann N Y Acad Sci"},{"key":"B75","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1111\/cei.12277","article-title":"Innate mucosal-associated invariant T (MAIT) cells are activated in inflammatory bowel diseases","volume":"176","author":"Serriari","year":"2014","journal-title":"Clin Exp Immunol"},{"key":"B76","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/nature13150","article-title":"Protective mucosal immunity mediated by epithelial CD1d and IL-10","volume":"509","author":"Olszak","year":"2014","journal-title":"Nature"},{"key":"B77","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1182\/blood-2012-06-432500","article-title":"Allogeneic hematopoietic cell transplantation for XIAP deficiency: an international survey reveals poor outcomes","volume":"121","author":"Marsh","year":"2013","journal-title":"Blood"},{"key":"B78","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.cyto.2013.09.007","article-title":"Sustained elevation of serum interleukin-18 and its association with hemophagocytic lymphohistiocytosis in XIAP deficiency","volume":"65","author":"Wada","year":"2014","journal-title":"Cytokine"},{"key":"B79","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1111\/cei.12306","article-title":"A new functional assay for the diagnosis of X-linked inhibitor of apoptosis (XIAP) deficiency","volume":"176","author":"Ammann","year":"2014","journal-title":"Clin Exp Immunol"},{"key":"B80","first-page":"205","article-title":"Dysgammaglobulinemia associated with Glu349del, a hypomorphic XIAP mutation","volume":"25","author":"Nishida","year":"2015","journal-title":"J Invest Allerg Clin"},{"key":"B81","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s10875-016-0348-4","article-title":"Hematopoietic stem cell transplantation for XIAP deficiency in Japan","volume":"37","author":"Ono","year":"2017","journal-title":"J Clin Immunol"},{"key":"B82","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1007\/s00431-019-03512-7","article-title":"X-linked lymphoproliferative syndrome in mainland China: review of clinical, genetic, and immunological characteristic","volume":"179","author":"Xu","year":"2020","journal-title":"Eur J Pediatr"},{"key":"B83","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1136\/gutjnl-2013-306520","article-title":"XIAP variants in male Crohn's disease","volume":"64","author":"Zeissig","year":"2015","journal-title":"Gut"},{"key":"B84","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.3748\/wjg.v24.i9.1035","article-title":"Phenotypic and genotypic characterization of inflammatory bowel disease in children under six years of age in China","volume":"24","author":"Fang","year":"2018","journal-title":"World J Gastroenterol"},{"key":"B85","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1097\/RHU.0000000000000327","article-title":"BIRC4 Mutation: an important rare cause of uveitis","volume":"21","author":"Basiaga","year":"2015","journal-title":"J Clin Rheumatol"},{"key":"B86","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1186\/s12887-015-0522-5","article-title":"The diagnostic challenge of very early-onset enterocolitis in an infant with XIAP deficiency","volume":"15","author":"Girardelli","year":"2015","journal-title":"BMC Pediatr"},{"key":"B87","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1007\/s10875-016-0320-3","article-title":"X-linked inhibitor of apoptosis complicated by Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) and granulomatous hepatitis","volume":"36","author":"Steele","year":"2016","journal-title":"J Clin Immunol"},{"key":"B88","doi-asserted-by":"publisher","first-page":"4966","DOI":"10.1182\/blood-2013-01-478735","article-title":"Successful stem cell transplant with antibody-based conditioning for XIAP deficiency with refractory hemophagocytic lymphohistiocytosis","volume":"121","author":"Worth","year":"2013","journal-title":"Blood"},{"key":"B89","doi-asserted-by":"publisher","first-page":"e198","DOI":"10.1097\/MPH.0000000000000191","article-title":"Complications of reduced intensity conditioning HSCT for XIAP deficiency (Alloimmune Cytopenias and HLH) successfully managed with donor lymphocyte infusion","volume":"37","author":"Varghese","year":"2015","journal-title":"J Pediatr Hematol Oncol"},{"key":"B90","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1007\/s10875-020-00795-6","article-title":"Haploidentical hematopoietic stem cell transplantation for XIAP deficiency: a single-center report","volume":"40","author":"Yang","year":"2020","journal-title":"J Clin Immunol"},{"key":"B91","doi-asserted-by":"publisher","first-page":"e13","DOI":"10.1097\/MPG.0000000000002297","article-title":"Risk-factors associated with poor outcomes in VEO-IBD secondary to XIAP deficiency: a case report and literature review","volume":"69","author":"Lekbua","year":"2019","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B92","doi-asserted-by":"publisher","first-page":"bcr2016216922","DOI":"10.26226\/morressier.57bc1755d462b80290b4d803","article-title":"XIAP deficiency and MEFV variants resulting in an autoinflammatory lymphoproliferative syndrome","volume":"2016","author":"Christiansen","year":"2016","journal-title":"BMJ Case Rep"},{"key":"B93","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.3892\/etm.2016.3498","article-title":"Successful allogeneic hematopoietic stem cell transplantation in a boy with X-linked inhibitor of apoptosis deficiency presenting with hemophagocytic lymphohistiocytosis: a case report","volume":"12","author":"Jiang","year":"2016","journal-title":"Exp Ther Med"},{"key":"B94","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1002\/pbc.25756","article-title":"Successful allogeneic hematopoietic stem cell transplantation in XIAP deficiency using reduced-intensity conditioning","volume":"63","author":"Chellapandian","year":"2016","journal-title":"Pediatr Blood Cancer"},{"key":"B95","doi-asserted-by":"publisher","first-page":"e13331","DOI":"10.1111\/tid.13331","article-title":"Inherited chromosomally integrated human herpesvirus-6 in a patient with XIAP deficiency","volume":"2020","author":"Inoue","year":"2020","journal-title":"Transpl Infect Dis."},{"key":"B96","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1055\/s-0033-1355393","article-title":"Clinical phenotype and functional analysis of a rare XIAP\/BIRC4 mutation","volume":"225","author":"Vieth","year":"2013","journal-title":"Klin Padiatr"},{"key":"B97","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/s12887-020-02075-z","article-title":"Eosinophilic colitis in a boy with a novel XIAP mutation: a case report","volume":"20","author":"Tang","year":"2020","journal-title":"BMC Pediatr"},{"key":"B98","doi-asserted-by":"publisher","first-page":"108495","DOI":"10.1016\/j.clim.2020.108495","article-title":"X-linked inhibitor of apoptosis protein deficiency complicated with Crohn's disease-like enterocolitis and Takayasu arteritis: a case report","volume":"217","author":"Takeuchi","year":"2020","journal-title":"Clin Immunol"},{"key":"B99","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1007\/s10875-017-0413-7","article-title":"IFN Block, Treosulfan conditioning and alphabeta T cell deplete PBSCT for XIAP-deficient HLH","volume":"37","author":"O'Rafferty","year":"2017","journal-title":"J Clin Immunol"},{"key":"B100","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1186\/s12876-015-0394-z","article-title":"A de novo whole gene deletion of XIAP detected by exome sequencing analysis in very early onset inflammatory bowel disease: a case report","volume":"15","author":"Kelsen","year":"2015","journal-title":"BMC Gastroenterol"},{"key":"B101","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1186\/s12887-020-02359-4","article-title":"Epstein-Barr virus-related hemophagocytic lymphohistiocytosis complicated with coronary artery dilation and acute renal injury in a boy with a novel X-linked inhibitor of apoptosis protein (XIAP) variant: a case report","volume":"20","author":"Chen","year":"2020","journal-title":"BMC Pediatr"},{"key":"B102","doi-asserted-by":"publisher","first-page":"198","DOI":"10.5152\/tpa.2014.1998","article-title":"Association of familial Mediterranean fever in Turkish children with inflammatory bowel disease","volume":"49","author":"Beser","year":"2014","journal-title":"Turk Pediatri Ars"},{"key":"B103","doi-asserted-by":"publisher","first-page":"e13019","DOI":"10.1097\/MD.0000000000013019","article-title":"Langerhans cell histiocytosis complicated with hemophagocytic lymphohistiocytosis in a boy with a novel XIAP mutation: a case report","volume":"97","author":"Guo","year":"2018","journal-title":"Medicine (Baltimore)"},{"key":"B104","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.humimm.2016.06.005","article-title":"Variable clinical phenotypes of X-linked lymphoproliferative syndrome in China: report of five cases with three novel mutations and review of the literature","volume":"77","author":"Jin","year":"2016","journal-title":"Hum Immunol"},{"key":"B105","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1111\/sji.12103","article-title":"Clinical and genetic features of 5 Chinese patients with X-linked lymphoproliferative syndrome","volume":"78","author":"Sun","year":"2013","journal-title":"Scand J Immunol"},{"key":"B106","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1093\/jpids\/piaa048","article-title":"A Novel X-Linked inhibitor of apoptosis deficient variant showing attenuated epstein-barr virus response","volume":"10","author":"Zhong","year":"2020","journal-title":"J Pediatric Infect Dis Soc."},{"key":"B107","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/j.jaci.2010.11.040","article-title":"Two new families with X-linked inhibitor of apoptosis deficiency and a review of all 26 published cases","volume":"127","author":"Horn","year":"2011","journal-title":"J Allergy Clin Immunol"},{"key":"B108","doi-asserted-by":"publisher","first-page":"e27593","DOI":"10.1002\/pbc.27593","article-title":"Different phenotypes of the same XIAP mutation in a family: a case of XIAP deficiency with juvenile idiopathic arthritis","volume":"66","author":"Shabani","year":"2019","journal-title":"Pediatr Blood Cancer"},{"key":"B109","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1053\/j.gastro.2014.07.023","article-title":"The diagnostic approach to monogenic very early onset inflammatory bowel disease","volume":"147","author":"Uhlig","year":"2014","journal-title":"Gastroenterology"},{"key":"B110","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1111\/bjh.12293","article-title":"Advances in understanding the pathogenesis of HLH","volume":"161","author":"Usmani","year":"2013","journal-title":"Br J Haematol"},{"key":"B111","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1002\/pbc.21039","article-title":"HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis","volume":"48","author":"Henter","year":"2007","journal-title":"Pediatr Blood Cancer"},{"key":"B112","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.it.2011.01.003","article-title":"Inflammasome activation and IL-1beta and IL-18 processing during infection","volume":"32","author":"van de Veerdonk","year":"2011","journal-title":"Trends Immunol"},{"key":"B113","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1136\/gutjnl-2013-306474","article-title":"XIAP deficiency is a mendelian cause of late-onset IBD","volume":"63","author":"Speckmann","year":"2014","journal-title":"Gut"},{"key":"B114","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1053\/j.gastro.2018.03.069","article-title":"Consequences of Identifying XIAP deficiency in an adult patient with inflammatory bowel disease","volume":"155","author":"Quaranta","year":"2018","journal-title":"Gastroenterology"},{"key":"B115","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.clim.2009.03.517","article-title":"Patients with X-linked lymphoproliferative disease due to BIRC4 mutation have normal invariant natural killer T-cell populations","volume":"132","author":"Marsh","year":"2009","journal-title":"Clin Immunol"},{"key":"B116","doi-asserted-by":"publisher","first-page":"e1000142","DOI":"10.1371\/journal.ppat.1000142","article-title":"XIAP regulates cytosol-specific innate immunity to Listeria infection","volume":"4","author":"Bauler","year":"2008","journal-title":"PLoS Pathog"},{"key":"B117","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1002\/cyto.b.20473","article-title":"A rapid flow cytometric screening test for X-linked lymphoproliferative disease due to XIAP deficiency","volume":"76","author":"Marsh","year":"2009","journal-title":"Cytometry B Clin Cytom"},{"key":"B118","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1111\/bjh.12386","article-title":"Treatment of Epstein Barr virus-induced haemophagocytic lymphohistiocytosis with rituximab-containing chemo-immunotherapeutic regimens","volume":"162","author":"Chellapandian","year":"2013","journal-title":"Br J Haematol"},{"key":"B119","doi-asserted-by":"publisher","first-page":"E25","DOI":"10.1111\/petr.12405","article-title":"Successful treatment of idiopathic colitis related to XIAP deficiency with allo-HSCT using reduced-intensity conditioning","volume":"19","author":"Tsuma","year":"2015","journal-title":"Pediatr Transplant"},{"key":"B120","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1182\/bloodadvances.2017004242","article-title":"IAPs protect host target tissues from graft-versus-host disease in mice","volume":"1","author":"Toubai","year":"2017","journal-title":"Blood Adv"},{"key":"B121","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1002\/eji.201847818","article-title":"XIAP deficiency in hematopoietic recipient cells drives donor T-cell activation and GvHD in mice","volume":"49","author":"Muller","year":"2019","journal-title":"Eur J Immunol"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2021.660520\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T04:22:50Z","timestamp":1623903770000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2021.660520\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,17]]},"references-count":121,"alternative-id":["10.3389\/fped.2021.660520"],"URL":"https:\/\/doi.org\/10.3389\/fped.2021.660520","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,17]]},"article-number":"660520"}}