Somatic mosaicism in B cells of a patient with autosomal dominant hyper IgE syndrome
Somatic mosaicism in B cells of a patient with autosomal dominant hyper IgE syndrome
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DOI：
10.1002/eji.201546275
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发表时间：
2016-10-01
影响因子：
5.4
通讯作者：
Santos-Argumedo, Leopoldo
中科院分区：
文献类型：
--
作者：
Alcantara-Montiel, Julio C.;Staines-Boone, Tamara;Santos-Argumedo, Leopoldo
高 IgE 综合征 (HIES) 的特点是反复出现皮肤脓肿、湿疹、肺炎和血清 IgE 水平升高。 HIES 的非免疫学表现包括特征性面部、病理性牙列、脊柱侧凸、骨骼改变、关节过度伸展和血管异常。体细胞嵌合是指一个个体中存在两个或多个具有不同基因型的细胞群。在本报告中，我们描述了一名患有经典 HIES 的患者和另一名具有轻度表型的患者，两人都携带相同的基因突变。轻度表型患者没有表现出特征性的面部特征，T CD4(+)细胞正常产生IL-17A，但B细胞中STAT-3磷酸化水平较低。有趣的是，在 B 细胞中发现的突变在分析的其他细胞类型中不存在，这与体细胞嵌合基因型的存在一致。这些患者之间观察到的临床和功能差异证明使用补充工具来更好地定义病例是合理的。这些方法可以更好地理解与体细胞嵌合体相关的复杂表型，并为分析 B 淋巴细胞在该疾病的病理生理学中的作用提供了可能性。这些知识不仅对治疗产生影响，而且对适当遗传咨询的提供也产生影响。
Hyper IgE syndrome (HIES) is characterized by recurrent skin abscesses, eczema, pneumonia, and high levels of serum IgE. Nonimmunologic manifestations of HIES include a characteristic face, pathologic dentition, scoliosis, bone alterations, hyperextensible joints, and vascular abnormalities. Somatic mosaicism is defined by the presence of two or more populations of cells with different genotypes in one individual. In this report, we describe one patient with classical HIES and another patient with a mild phenotype, both harboring the same genetic mutation. The patient with a mild phenotype did not present the characteristic face, had normal production of IL-17A by T CD4(+) cells, but had low phosphorylation of STAT-3 in B cells. Interestingly, the mutation found in B cells was absent in other cell types analyzed, in agreement with the presence of a somatic mosaic genotype. The clinical and functional differences observed between these patients justify the use of complementary tools for a better definition of the cases. These approaches allow for a better understanding of complex phenotypes associated with somatic mosaicisms, and present the possibility to analyze the role of B lymphocytes in the pathophysiology of this disease. This knowledge has an impact on not only the treatment but also the provision of appropriate genetic counseling.