PDF(Pubmed)
Abstract：
X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia (XMEN) disease are caused by deficiency of the magnesium transporter 1 (MAGT1) gene. We studied 23 patients with XMEN, 8 of whom were EBV naive. We observed lymphadenopathy (LAD), cytopenias, liver disease, cavum septum pellucidum (CSP), and increased CD4-CD8-B220-TCRαβ+ T cells (αβDNTs), in addition to the previously described features of an inverted CD4/CD8 ratio, CD4+ T lymphocytopenia, increased B cells, dysgammaglobulinemia, and decreased expression of the natural killer group 2, member D (NKG2D) receptor. EBV-associated B cell malignancies occurred frequently in EBV-infected patients. We studied patients with XMEN and patients with autoimmune lymphoproliferative syndrome (ALPS) by deep immunophenotyping (32 immune markers) using time-of-flight mass cytometry (CyTOF). Our analysis revealed that the abundance of 2 populations of naive B cells (CD20+CD27-CD22+IgM+HLA-DR+CXCR5+CXCR4++CD10+CD38+ and CD20+CD27-CD22+IgM+HLA-DR+CXCR5+CXCR4+CD10-CD38-) could differentially classify XMEN, ALPS, and healthy individuals. We also performed glycoproteomics analysis on T lymphocytes and show that XMEN disease is a congenital disorder of glycosylation that affects a restricted subset of glycoproteins. Transfection of MAGT1 mRNA enabled us to rescue proteins with defective glycosylation. Together, these data provide new clinical and pathophysiological foundations with important ramifications for the diagnosis and treatment of XMEN disease.
摘要：
X连锁免疫缺陷与镁缺陷，EBV感染,和瘤形成（XMEN）疾病是由镁转运蛋白1（MAGT1）基因缺乏引起的。我们研究了23例XMEN患者，其中8人是EBV天真。我们观察到淋巴结病（LAD），血细胞减少,肝病,透明隔腔（CSP），和增加的CD4-CD8-B220-TCRαβ+T细胞（αβDNTs），除了先前描述的CD4/CD8比值倒置的特征外，CD4+T淋巴细胞减少症,B细胞增多,丙种球蛋白血症,天然杀伤组2成员D(NKG2D)受体的表达下降。EBV相关的B细胞恶性肿瘤经常发生在EBV感染的患者中。我们使用飞行时间质量细胞计数（CyTOF）通过深度免疫表型（32种免疫标记）研究了XMEN患者和自身免疫性淋巴增生综合征（ALPS）患者。我们的分析表明，2个幼稚B细胞群（CD20CD27-CD22IgMHLA-DRCXCR5CXCR4++CD10CD38和CD20CD27-CD22IgMHLA-DRCXCR5CXCR4CD10-CD38-）的丰度可以对XMEN进行差异分类。阿尔卑斯,和健康的个体。我们还对T淋巴细胞进行了糖蛋白质组学分析，并显示XMEN病是一种先天性糖基化障碍，影响糖蛋白的有限子集。MAGT1mRNA的转染使我们能够拯救具有糖基化缺陷的蛋白质。一起,这些数据为XMEN疾病的诊断和治疗提供了新的临床和病理生理学基础，具有重要的影响。
