Mudde Anne C A, Booth Claire, Marsh Rebecca A
Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
Department of Immunology and Gene Therapy, Great Ormond Street Hospital, London, United Kingdom.
Front Pediatr. 2021 Jun 17;9:660520. doi: 10.3389/fped.2021.660520. eCollection 2021.
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.
X连锁凋亡抑制蛋白（XIAP）缺乏症是一种罕见的先天性免疫缺陷病，于2006年首次被描述。XIAP缺乏症的特征是免疫调节异常和广泛的临床表现，包括噬血细胞性淋巴组织细胞增生症（HLH）、炎症性肠病（IBD）、低丙种球蛋白血症、易感染、脾肿大、血细胞减少以及其他不太常见的自身炎症现象。自该疾病首次被描述以来，已鉴定出许多XIAP缺乏症患者，我们对该疾病的认识也有所增加。已描述了90多种致病突变，现在更多的炎症性疾病表现，如肝炎、关节炎和葡萄膜炎，已得到充分认识。最近，在引入减低强度预处理（RIC）后，异基因造血干细胞移植（HSCT）作为XIAP缺乏症唯一的治愈性治疗选择，其疗效有所改善。XIAP缺乏症的病理生理学尚未完全了解，然而已知XIAP在先天性和适应性免疫反应以及免疫调节中均发挥作用，最显著的是通过调节肿瘤坏死因子（TNF）受体信号传导和NLRP3炎性小体活性。在本综述中，我们将提供XIAP缺乏症临床方面和病理生理学的最新概述。
