X-linked ectodermal dysplasia and immunodeficiency caused by reversion mosaicism of NEMO reveals a critical role for NEMO in human T-cell development and/or survival
X-linked ectodermal dysplasia and immunodeficiency caused by reversion mosaicism of NEMO reveals a critical role for NEMO in human T-cell development and/or survival
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DOI：
10.1182/blood-2003-10-3655
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发表时间：
2004-06-15
期刊：
影响因子：
20.3
通讯作者：
Nakahata, T
中科院分区：
文献类型：
--
作者：
Nishikomori, R;Akutagawa, H;Nakahata, T
X连锁外胚层发育不良和免疫缺陷（XL-EDA-ID）是由核因子-κ B（NF-κ B）必需调节因子（NEMO）突变引起的X连锁隐性疾病。在这里，我们报告了一个XL-EDA-ID患者具有非常少的幼稚表型T细胞和有丝分裂原诱导的外周血单核细胞（PBMC）增殖缺陷的非典型特征。通过细胞内NEMO染色的流式细胞术分析诊断患者的NEMO缺陷。特定细胞谱系（单核细胞和中性粒细胞）表达降低水平的NEMO，但检测到2个群体的T、B和NK细胞的NEMO表达正常和降低。基因组分析表明，重复的4.4 kb的序列范围从内含子3到外显子6导致NEMO的表达减少。多态性分析表明，患者的B-和T-细胞系与新的表达减少和正常的体细胞嵌合体不是由于母胎输血，但最有可能是由于合子后回复。这个XL-EDA-ID病例增加了我们对NEMO生物学的理解，表明NEMO对人类和小鼠的T细胞发育和/或存活至关重要。
X-linked ectodermal dysplasia and immunodeficiency (XL-EDA-ID) is an X-linked recessive disease caused by a mutation in the nuclear factor-kappaB (NF-kappaB) essential modulator (NEMO). Here we report an XL-EDA-ID patient with atypical features of very few naive-phenotype T cells and defective mitogen-induced proliferation of peripheral blood mononuclear cells (PBMCs). The patient's NEMO defect was diagnosed by flow cytometric analysis of intracellular NEMO staining. Specific cell lineages (monocytes and neutrophils) expressed reduced levels of NEMO, but 2 populations of T, B, and NK cells were detected with normal and reduced expression of NEMO. Genomic analysis revealed that duplication of a 4.4-kb sequence ranging from intron 3 to exon 6 caused the reduced expression of NEMO. Polymorphism analysis showed that the patient's B- and T-cell lines with reduced and normal expression of NEW had the somatic mosaicism was not due to fetomaternal transfusion but was most likely due to postzygotic reversion. This XL-EDA-ID case adds to our understanding of NEMO biology, indicating that NEMO is critical for T-cell development and/or survival in humans as well as in mice.