Dedicator of cytokinesis 8 (DOCK8) deficiency.
Dedicator of cytokinesis 8 (DOCK8) deficiency.
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DOI：
10.1097/aci.0b013e32833fd718
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发表时间：
2010-12
影响因子：
2.8
通讯作者：
Su HC
中科院分区：
文献类型：
--
作者：
Su HC
本综述的目的是描述一种新的联合原发性免疫缺陷疾病，以前称为常染色体隐性高ige综合征，其分子基础于2009年被发现。两组在至少30例先前被诊断为非典型型高ige综合征的患者中发现了DOCK8（细胞分裂献身者8）基因的纯合和复合杂合功能丧失突变。DOCK8表达缺失会损害T细胞体外扩增，这可能有助于解释在这些患者中观察到的T细胞淋巴细胞减少和对皮肤病毒感染的易感性。在Dock8缺失的小鼠模型中，Dock8表达缺失也会损害针对特定抗原的持久二抗反应的产生，这可能解释了在患者中观察到的功能性抗体异常和复发性肺感染。2例同种异体造血细胞清髓移植术后感染并发症治愈。这种疾病的分子基础的发现有望促进诊断和明确的治疗与造血细胞移植。需要进一步的研究来了解DOCK8在淋巴细胞中的正常功能以及DOCK8缺乏如何导致疾病。
The purpose of this review is to describe a new combined primary immunodeficiency disease, previously known as autosomal recessive hyper-IgE syndrome, whose molecular basis was discovered in 2009. Two groups identified homozygous and compound heterozygous loss-of-function mutations in the DOCK8 (Dedicator of cytokinesis 8) gene in at least 30 patients who had been previously diagnosed with an atypical form of hyper-IgE syndrome. Absence of DOCK8 expression impairs T cell expansion in vitro, which could help explain the T cell lymphopenia and susceptibility to cutaneous viral infections observed in these patients. In mouse models of Dock8 deficiency, absence of DOCK8 expression also impairs the generation of a durable secondary antibody response to specific antigens, which could account for the functional antibody abnormalities and recurrent sinopulmonary infections observed in the patients. Two patients have been cured of infectious complications after myeloablative allogeneic hematopoietic cell transplantation. The discovery of the molecular basis of this disease is expected to facilitate diagnosis and definitive treatment with hematopoietic cell transplantation. Further research is needed to understand how DOCK8 normally functions in lymphocytes and how DOCK8 deficiency leads to disease.