Cohen Jeffrey I, Dropulic Lesia, Hsu Amy P, Zerbe Christa S, Krogmann Tammy, Dowdell Kennichi, Hornung Ronald L, Lovell Jana, Hardy Nancy, Hickstein Dennis, Cowen Edward W, Calvo Katherine R, Pittaluga Stefania, Holland Steven M
Laboratorie of Infectious Diseases.
Laboratorie of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases.
Clin Infect Dis. 2016 Jul 1;63(1):41-7. doi: 10.1093/cid/ciw160. Epub 2016 May 11.
Most patients infected with Epstein-Barr virus (EBV) are asymptomatic, have nonspecific symptoms, or have self-limiting infectious mononucleosis. EBV, however, may result in severe primary disease or cancer.
We report EBV diseases associated with GATA2 deficiency at one institution and describe the hematology, virology, and cytokine findings.
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 α, interferon γ, and interferon gamma-induced protein 10 were higher in patients with GATA2 deficiency than in controls.
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.
大多数感染爱泼斯坦-巴尔病毒（EBV）的患者无症状、有非特异性症状或患有自限性传染性单核细胞增多症。然而，EBV可能导致严重的原发性疾病或癌症。
我们报告了在一家机构中与GATA2缺乏相关的EBV疾病，并描述了血液学、病毒学和细胞因子的研究结果。
7例GATA2缺乏患者发生了严重的EBV疾病。3例表现为需要住院治疗的EBV传染性单核细胞增多症，1例患有慢性活动性EBV疾病（B细胞型），1例患有伴有噬血细胞性淋巴组织细胞增生症的EBV相关种痘样水疱病样淋巴瘤，2例患有EBV阳性平滑肌瘤。7例患者中有4例有严重疣，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、CD4 T细胞和自然杀伤细胞数量均较低。所有患者血液中的EBV水平均升高；3例接受检测的患者中有2例血液中EBV主要即刻早期基因表达，提示EBV活跃的裂解感染。GATA2缺乏患者的血浆肿瘤坏死因子α、干扰素γ和干扰素γ诱导蛋白10的平均水平高于对照组。
GATA2是第一个与EBV种痘样水疱病样淋巴瘤相关的基因。对于严重的原发性EBV感染或EBV相关癌症患者，尤其是那些患有播散性非结核分枝杆菌病和疣的患者，应考虑GATA2缺乏。
