Establishment of novel diagnostic parameters for the early therapeutic intervention of EBV-associated lymphoproliferative diseases.

EBV-HLH的特点是严重的细胞分裂素血症和细胞减少，经常导致侵袭性恶化和致命结局。最重要的是做出正确的诊断并尽快开始治疗干预，因为治疗的延误可能会在几个小时内对重要器官造成不可逆转的损害。我们现在了解到，EBV-HLH的基本发病机制是选择性地激活和扩增异位感染的CD8^+T细胞克隆。因此，通过确定EBV感染的靶点，并证明EBV感染细胞的克隆性，可以做出明确的诊断。在本研究中，我们分析了感染的CD8~+T细胞表面抗原表达和血清细胞因子的变化。根据这些结果，我们试图建立一种简化的方法来建立EBV-HLH早期诊断的参数。正如预期的那样，在大多数EB病毒感染病例中，EB病毒感染局限于CD8+T细胞的单个克隆，表达特定的TCRVβ。CDR3大小分布分析表明，这些细胞为单克隆细胞。异常克隆表现为高水平的HLA-DR和低水平的CD5。因此，EBV感染的细胞被鉴定为CD8^+T细胞中的HLA-DR^++CD5^-细胞群。进一步的分析表明，在包括EBV在内的急性病毒感染期间，FHL2患者中也观察到了类似的细胞群。

EBV-HLH is characterized by extreme cytokinemia and cytopenia, frequently leading to aggressive deterioration and fatal outcome. It is of paramount importance to make correct diagnosis and start therapeutic intervention as soon as possible, as the delay in the treatment may result in irreversible damage to vital organs within several hours. We now understand that the essential pathogenesis of EBV-HLH is selective activation and expansion of an ectopically EBV-infected CD8^+T cell clone. Thus the definitive diagnosis of EBV-HLH can be made by identifying the target of EBV infection and by proving the clonality of the EBV-infected cells.In this study, we analyzed the profiles of surface antigen expression of the infected CD8^+T cells and serum cytokines. With these results, we tried to establish a simplified method to establish parameters for the early diagnosis of EBV-HLH. As was expected, EBV infection in most cases of EBV-HLH was confined to a single clone of CD8+T cells, expressing a particular TCR Vβ. CDR3 size distribution analysis indicates that these cells are of a single clone. The abnormal clones exhibited high levels of HLA-DR and decreased levels of CD5. Therefore, EBV-infected cells were identifiable as HLA-DR^++CD5^-cell population within CD8^+T cells. Further analysis revealed that similar cell population was observed in patients with FHL2 during acute viral infection, including EBV.