XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus
XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus
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DOI：
10.1182/blood-2013-11-538686
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发表时间：
2014-04-03
期刊：
影响因子：
20.3
通讯作者：
Lenardo, Michael J.
中科院分区：
文献类型：
--
作者：
Li, Feng-Yen;Chaigne-Delalande, Benjamin;Lenardo, Michael J.
EB 病毒 (EBV) 是一种致癌性伽马疱疹病毒，可感染全世界 95% 的成年人并持续存在，并有可能在免疫功能低下的宿主中引起致命疾病，尤其是淋巴瘤。易患 EBV 相关恶性肿瘤的原发性免疫缺陷 (PID) 为了解 EBV 免疫防御的分子机制提供了新的见解。我们最近描述了一种新型 PID，现已命名为“X 连锁免疫缺陷伴镁缺陷、EB 病毒感染和瘤形成”(XMEN) 疾病，其特征是编码镁转运蛋白 1 (MAGT1) 的基因功能丧失突变、慢性高水平 EBV 伴 EBV 感染 B 细胞增加，以及对 EBV 相关淋巴瘤的易感性增加。 XMEN 疾病的遗传病因学揭示了细胞内游离镁在免疫功能中的意想不到的定量作用，并导致了新的诊断和治疗策略。在这里，我们回顾了这种以前未被认识的疾病的临床表现、基因突变谱、发病机制的分子机制以及诊断和治疗注意事项。
Epstein-Barr virus (EBV) is an oncogenic gammaherpesvirus that infects and persists in 95% of adults worldwide and has the potential to cause fatal disease, especially lymphoma, in immunocompromised hosts. Primary immunodeficiencies (PIDs) that predispose to EBV-associated malignancies have provided novel insights into the molecular mechanisms of immune defense against EBV. We have recently characterized a novel PID now named "X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia" (XMEN) disease characterized by loss-of-function mutations in the gene encoding magnesium transporter 1 (MAGT1), chronic high-level EBV with increased EBV-infected B cells, and heightened susceptibility to EBV-associated lymphomas. The genetic etiology of XMEN disease has revealed an unexpected quantitative role for intracellular free magnesium in immune functions and has led to novel diagnostic and therapeutic strategies. Here, we review the clinical presentation, genetic mutation spectrum, molecular mechanisms of pathogenesis, and diagnostic and therapeutic considerations for this previously unrecognized disease.