Vistarop Aldana, Jimenez Oscar, Cohen Melina, De Matteo Elena, Preciado Maria Victoria, Chabay Paola
Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA. Molecular Biology Laboratory, Pathology Division, Ricardo Gutiérrez Children's Hospital, Buenos Aires C1425EFD, Argentina.
Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA. Pathology Division, Ricardo Gutiérrez Children's Hospital, Buenos Aires C1425EFD, Argentina.
Pathogens. 2020 Jan 19;9(1):68. doi: 10.3390/pathogens9010068.
In Argentina, Epstein-Barr virus (EBV) presence is associated with Hodgkin lymphoma (HL) in patients younger than 10 years, suggesting a relationship between low age of EBV infection and HL. Given that HL is derived from germinal centers (GC), our aim was to compare EBV protein expression and microenvironment markers between pediatric HL patients and EBV+GC in children.
EBV presence and immune cell markers were assessed by in situ hybridization and immunohistochemistry (IHC).
Viral latency II pattern was proved in all HL patients and in 81.8% of EBV+ tonsillar GCs. LMP1 and LMP2 co-expression were proved in 45.7% HL cases, but only in 7.7% EBV+ GC in pediatric tonsils. An increase in CD4+, IL10, and CD68+ cells was observed in EBV+ GC. In pediatric HL patients, only the mean of IL10+ cells was statistically higher in EBV+ HL.
Our findings point us out to suggest that LMP1 expression may be sufficient to drive neoplastic transformation, that an immune regulatory milieu counteracts cytotoxic environment in EBV-associated Hodgkin lymphoma, and that CD4+ and CD68+ cells may be recruited to act in a local collaborative way to restrict, at least in part, viral-mediated lymphomagenesis in tonsillar GC.
在阿根廷，10岁以下患者中，爱泼斯坦-巴尔病毒（EBV）的存在与霍奇金淋巴瘤（HL）相关，这表明EBV感染的低龄与HL之间存在关联。鉴于HL起源于生发中心（GC），我们的目的是比较儿童HL患者与儿童EBV+GC之间的EBV蛋白表达和微环境标志物。
通过原位杂交和免疫组织化学（IHC）评估EBV的存在和免疫细胞标志物。
在所有HL患者和81.8%的EBV+扁桃体GC中证实了病毒潜伏II型模式。在45.7%的HL病例中证实了LMP1和LMP2共表达，但在儿童扁桃体的EBV+GC中仅为7.7%。在EBV+GC中观察到CD4+、IL10和CD68+细胞增加。在儿童HL患者中，仅EBV+HL中IL10+细胞的平均值在统计学上更高。
我们的研究结果表明，LMP1表达可能足以驱动肿瘤转化，免疫调节环境可抵消EBV相关霍奇金淋巴瘤中的细胞毒性环境，并且CD4+和CD68+细胞可能被募集以局部协作的方式发挥作用，至少部分限制扁桃体GC中病毒介导的淋巴瘤发生。
