Tanita Kay, Hoshino Akihiro, Imadome Ken-Ichi, Kamiya Takahiro, Inoue Kento, Okano Tsubasa, Yeh Tzu-Wen, Yanagimachi Masakatsu, Shiraishi Akira, Ishimura Masataka, Schober Tilmann, Rohlfs Meino, Takagi Masatoshi, Imai Kohsuke, Takada Hidetoshi, Ohga Shouichi, Klein Christoph, Morio Tomohiro, Kanegane Hirokazu
Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Advanced Medicine for Virus Infections, National Center for Child Health and Development, Tokyo, Japan.
Front Pediatr. 2019 Feb 4;7:15. doi: 10.3389/fped.2019.00015. eCollection 2019.
Chronic active Epstein-Barr virus (EBV) infection (CAEBV) is an EBV-associated lymphoproliferative disease characterized by repeated or sustainable infectious mononucleosis (IM)-like symptoms. EBV is usually detected in B cells in patients who have IM or Burkitt's lymphoma and even in patients with X-linked lymphoproliferative syndrome, which is confirmed to have vulnerability to EBV infection. In contrast, EBV infects T cells (CD4 T, CD8 T, and γδT) or NK cells mono- or oligoclonally in CAEBV patients. It is known that the CAEBV phenotypes differ depending on which cells are infected with EBV. CAEBV is postulated to be associated with a genetic immunological abnormality, although its cause remains undefined. Here we describe a case of EBV-related γδT-cell proliferation with underlying hypomorphic mutation. The immunological phenotype consisted of γδT-cell proliferation in the peripheral blood. A presence of EBV-infected B cells and γδT cells mimicked γδT-cell-type CAEBV. Although the patient had normal expression of CD132 (common γ chain), the phosphorylation of STAT was partially defective, indicating impaired activation of the downstream signal of the JAK/STAT pathway. Although the patient was not diagnosed as having CAEBV, this observation shows that CAEBV might be associated with immunological abnormality.
慢性活动性EB病毒（EBV）感染（CAEBV）是一种与EBV相关的淋巴增殖性疾病，其特征为反复或持续出现类似传染性单核细胞增多症（IM）的症状。EBV通常在患有IM或伯基特淋巴瘤的患者的B细胞中被检测到，甚至在已证实易受EBV感染的X连锁淋巴增殖综合征患者中也能检测到。相比之下，在CAEBV患者中，EBV单克隆或寡克隆感染T细胞（CD4 T细胞、CD8 T细胞和γδT细胞）或自然杀伤（NK）细胞。已知CAEBV的表型因感染EBV的细胞类型而异。尽管CAEBV的病因尚不清楚，但推测其与遗传免疫异常有关。在此，我们描述了一例伴有潜在低表达突变的EBV相关γδT细胞增殖病例。免疫表型表现为外周血中γδT细胞增殖。EBV感染的B细胞和γδT细胞的存在类似于γδT细胞型CAEBV。尽管该患者CD132（共同γ链）表达正常，但信号转导和转录激活因子（STAT）的磷酸化存在部分缺陷，表明Janus激酶/信号转导和转录激活因子（JAK/STAT）途径的下游信号激活受损。尽管该患者未被诊断为CAEBV，但这一观察结果表明CAEBV可能与免疫异常有关。
