Familial hypereosinophilia associated with eosinophilic gastrointestinal symptoms in individuals with a missense mutation in CKLF-like MARVEL transmembrane domain containing 3.
Familial hypereosinophilia associated with eosinophilic gastrointestinal symptoms in individuals with a missense mutation in CKLF-like MARVEL transmembrane domain containing 3.
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在含有 3 的 CKLF 样 MARVEL 跨膜结构域中存在错义突变的个体中，家族性嗜酸性粒细胞增多与嗜酸性胃肠道症状相关。
DOI：
10.1111/cea.13957
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Wardlaw AJ
中科院分区：
文献类型：
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作者：
Wardlaw AJ
持续性原因不明的嗜酸性粒细胞增多症是相对少见的，有许多原因，其中过敏和蠕虫寄生虫感染是最常见的诊断。不太常见的原因包括特发性嗜酸性粒细胞增多综合征（HES）、嗜酸性肉芽肿伴多血管炎（EGPA）和单器官疾病，如嗜酸性粒细胞性胃肠病（EGID）。[1]虽然在大多数情况下，嗜酸性粒细胞增多症偶尔由骨髓增生性肿瘤引起，但它是由于旁观者细胞过度产生生长因子，特别是白细胞介素-5，这些旁观者细胞通常是淋巴细胞。有时环境因素可以被识别，但嗜酸性粒细胞增多症的根本原因往往仍然不清楚。嗜酸性粒细胞疾病引起的症状模式是可变的，从单一器官到多系统受累，从偶发性和轻度到持续性和危及生命，特别是如果有心脏受累。肺、皮肤和胃肠道是最常见的受累系统，尽管血栓形成、嗜酸性心内膜心肌炎和周围神经病变是潜在的改变生命的并发症。胃肠道的任何部分都可能受到小肠粘膜嗜酸性粒细胞增加的影响，这是诊断嗜酸性胃肠炎（EG）的核心标准。3嗜酸性粒细胞性疾病的主要治疗方法是全身性皮质类固醇，尽管靶向嗜酸性粒细胞的特定治疗方法的出现，如生物治疗，包括拮抗白细胞介素（IL）-5途径的美泊利珠单抗，瑞利珠单抗和贝那利珠单抗，提供了新的治疗选择，副作用风险较低。[4]几乎所有的嗜酸性粒细胞增多症都是散发的，没有任何家族性的迹象。Klion及其同事描述的一个大型家族已被证明是由于IL-5的过量产生造成的，尽管所涉及的确切基因尚未确定。5在这篇论文中，我们描述了4名患有家族性嗜酸性粒细胞增多症的受试者，其具有明显的常染色体显性遗传模式和主要的胃肠道症状，其中我们确定了CKLF样MARVEL跨膜结构域3（CMTM 3）作为候选基因。
To the Editor, A persistent unexplained eosinophilia is relatively unusual and has a number of causes of which allergy and infection with helminthic parasites are the most common diagnoses. Less common causes include idiopathic hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA) and single-organ conditions such as eosinophilic gastrointestinal disease (EGID). 1 Although occasionally caused by myeloproliferative neoplasm in most cases, eosinophilia is due to excess production of growth factors, particularly interleukin-5, by bystander cells which are often lymphoid in nature. Sometimes an environmental trigger can be identified, but the underlying cause of the eosinophilia often remains obscure. The pattern of symptoms caused by eosinophilic disease is variable, ranging from single-organ to multisystem involvement and from episodic and mild, to persistent and life-threatening, particularly if there is cardiac involvement. 2 The lungs, skin and gastrointestinal tract are the most commonly involved systems, although thrombophilia, eosinophilic endomyocarditis and peripheral neuropathy are potentially life-changing complications. Any part of the gastrointestinal tract can be affected with an increase in mucosal eosinophils in the small intestine, a core criterion for a diagnosis of eosinophilic gastroenteritis (EG). 3 The mainstay of treatment of eosinophilic disease is systemic corticosteroids, although the advent of specific therapies that target eosinophils such as the biological therapies, involving mepolizumab, reslizumab and benralizumab that antagonise the interleukin (IL)-5 pathway, offers novel management options with a lower risk of side effects. 4 Virtually all cases of eosinophilia are sporadic without any suggestion of a familial component. One large kindred described by Klion and colleagues has been shown to be due to excess production of IL-5, although the exact gene involved has not yet been identified. 5 In this paper we describe four subjects with a familial type of hypereosinophilia with an apparent autosomal dominant pattern of inheritance and predominantly gastrointestinal symptoms, where we have identified CKLF-like MARVEL transmembrane domain containing 3 (CMTM3), as a candidate gene.