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.
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http://dx.doi.org/10.3389/fped.2021.660520 | DOI Listing |
Gastroenterology
October 2024
Paediatric Gastroenterology, Great Ormand Street Hospital, London, United Kingdom; Juliet Keidan Institute of Pediatric Gastroenterology, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel. Electronic address:
Eur J Pediatr
December 2024
Institute for Maternal and Child Health (IRCCS) "Burlo Garofolo", Via Dell' Istria 65, 34137, Trieste, Italy.
Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) in children with inflammatory bowel disease (IBD) has been reported only anecdotally. This study aimed at describing the clinical features and outcomes of children diagnosed with both IBD and HLH/MAS. Data on IBD and HLH/MAS characteristics, biochemical, microbiological and genetic assessments, treatments, and outcomes were collected from the Italian Pediatric IBD Registry and presented using descriptive statistics.
View Article and Find Full Text PDFClin Exp Immunol
July 2024
Laboratory of Clinical Immunology, Inflammation and Allergies (LICIA), Faculty of Medicine and Pharmacy, Hassan II University, Casablanca 20250, Morocco.
Cureus
June 2024
Internal Medicine, Hackensack University Medical Center, Hackensack, USA.
Blood
September 2024
Cell Biology Program, SickKids Research Institute, Toronto, ON, Canada.
Deficiency of X-linked inhibitor of apoptosis protein (XIAP) is a rare genetic condition that can present with recurrent episodes of hemophagocytic lymphohistiocytosis (HLH), though the exact mechanisms leading to this hyperinflammatory disorder are unclear. Understanding its biology is critical to developing targeted therapies for this potentially fatal disease. Here, we report on a novel multiexonic intragenic duplication leading to XIAP deficiency with recurrent HLH that demonstrated complete response to interleukin (IL)-1β blockade.
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