Epstein-Barr Virus Susceptibility in Activated PI3Kδ Syndrome (APDS) Immunodeficiency.
Epstein-Barr Virus Susceptibility in Activated PI3Kδ Syndrome (APDS) Immunodeficiency.
复制标题
Epstein-Barr病毒在活化的PI3Kδ综合征（APDS）免疫缺陷中的敏感性。
DOI：
10.3389/fimmu.2017.02005
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发表时间：
2017
影响因子：
7.3
通讯作者：
Lucas CL
中科院分区：
文献类型：
--
作者：
Carpier JM;Lucas CL
活化PI3Kδ综合征（Activated PI3Kδ Syndrome， APDS）是一种遗传性免疫疾病，由编码磷酸肌肽3-激酶δ (PI3Kδ)亚基p110δ或p85δ的基因杂合性功能获得突变引起。这种新近描述的原发性免疫缺陷疾病（PID）的特征是复发性肺感染、淋巴细胞增殖和对疱疹病毒的易感性，以eb病毒（EBV）感染最为显著。广泛的PIDs具有不同的、分子定义的遗传病因，可引起EBV、淋巴增生性疾病和淋巴瘤的易感性。历史上，功能缺失突变导致细胞介导的细胞毒性或抗原受体信号传导缺陷的PID患者被发现极易发生病理性EBV感染。相比之下，在APDS患者中观察到的PI3K信号功能的增加自相矛盾地使这些患者易患EBV，尽管其潜在机制尚不完全清楚。在细胞水平上，APDS患者表现出紊乱的B淋巴细胞发育和类开关重组缺陷，这通常导致免疫球蛋白产生缺陷。此外，APDS患者也表现出T细胞向端粒短的末端效应物和衰老标记物的异常倾斜。在这里，我们回顾APDS，特别关注这些患者的淋巴细胞生物学改变如何赋予EBV易感性。
Activated PI3Kδ Syndrome (APDS) is an inherited immune disorder caused by heterozygous, gain-of-function mutations in the genes encoding the phosphoinositide 3-kinase delta (PI3Kδ) subunits p110δ or p85δ. This recently described primary immunodeficiency disease (PID) is characterized by recurrent sinopulmonary infections, lymphoproliferation, and susceptibility to herpesviruses, with Epstein–Barr virus (EBV) infection being most notable. A broad range of PIDs having disparate, molecularly defined genetic etiology can cause susceptibility to EBV, lymphoproliferative disease, and lymphoma. Historically, PID patients with loss-of-function mutations causing defective cell-mediated cytotoxicity or antigen receptor signaling were found to be highly susceptible to pathological EBV infection. By contrast, the gain of function in PI3K signaling observed in APDS patients paradoxically renders these patients susceptible to EBV, though the underlying mechanisms are incompletely understood. At a cellular level, APDS patients exhibit deranged B lymphocyte development and defects in class switch recombination, which generally lead to defective immunoglobulin production. Moreover, APDS patients also demonstrate an abnormal skewing of T cells toward terminal effectors with short telomeres and senescence markers. Here, we review APDS with a particular focus on how the altered lymphocyte biology in these patients may confer EBV susceptibility.