Association of GATA2 Deficiency With Severe Primary Epstein-Barr Virus (EBV) Infection and EBV-associated Cancers
Association of GATA2 Deficiency With Severe Primary Epstein-Barr Virus (EBV) Infection and EBV-associated Cancers
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DOI：
10.1093/cid/ciw160
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发表时间：
2016-07-01
影响因子：
11.8
通讯作者：
Holland, Steven M.
中科院分区：
文献类型：
--
作者：
Cohen, Jeffrey I.;Dropulic, Lesia;Holland, Steven M.
背景大多数感染EB病毒（EBV）的患者无症状，有非特异性症状，或有自我模仿的传染性单核细胞增多症。然而，EBV可导致严重的原发性疾病或癌症。我们报告了一个机构中与GATA 2缺乏相关的EB病毒疾病，并描述了血液学、病毒学和细胞因子的发现。7例GATA 2缺乏症患者发生了严重的EBV疾病。3例EBV感染性单核细胞增多症需要住院治疗，1例慢性活动性EBV疾病（B细胞型），1例EBV相关性种痘样水肿样淋巴瘤伴噬血细胞性淋巴组织细胞增多症，2例EBV阳性平滑肌肿瘤。7例患者中有4例有严重的疣，3例有播散性非结核分枝杆菌感染。所有患者的单核细胞、B细胞、CD 4 T细胞和自然杀伤细胞数量均较低。所有患者血液中EBV水平均升高; 3例受试患者中有2例血液中EBV主要立即早期基因表达，表明活动性EBV裂解性感染。平均血浆肿瘤坏死因子a，干扰素，GATA 2缺陷患者血清IFN-γ诱导蛋白10水平高于对照组。GATA 2是第一个与EBV痘样水肿样淋巴瘤相关的基因。严重原发性EBV感染或EBV相关癌症患者，尤其是播散性非结核分枝杆菌病和疣患者，应考虑GATA 2缺乏。
Background. Most patients infected with Epstein-Barr virus (EBV) are asymptomatic, have nonspecific symptoms, or have self-imiting infectious mononucleosis. EBV, however, may result in severe primary disease or cancer.Methods. We report EBV diseases associated with GATA2 deficiency at one institution and describe the hematology, virology, and cytokine findings.Results. Seven patients with GATA2 deficiency developed severe EBV disease. Three presented with EBV infectious mononucleosis requiring hospitalization, 1 had chronic active EBV disease (B-cell type), 1 had EBV-associated hydroa vacciniforme-like lymphoma with hemophagocytic lymphohistiocytosis, and 2 had EBV-positive smooth muscle tumors. Four of the 7 patients had severe warts and 3 had disseminated nontuberculous mycobacterial infections. All of the patients had low numbers of monocytes, B cells, CD4 T cells, and natural killer cells. All had elevated levels of EBV in the blood; 2 of 3 patients tested had expression of the EBV major immediate-early gene in the blood indicative of active EBV lytic infection. Mean plasma levels of tumor necrosis factor a, interferon., and interferon gamma-induced protein 10 were higher in patients with GATA2 deficiency than in controls.Conclusions. GATA2 is the first gene associated with EBV hydroa vacciniforme-like lymphoma. GATA2 deficiency should be considered in patients with severe primary EBV infection or EBV-associated cancer, especially in those with disseminated nontuberculous mycobacterial disease and warts.