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

EBV-HLH的特征是极端的细胞因子血症和血细胞减少，经常导致侵袭性恶化和致命的结果。最重要的是要做出正确的诊断，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的基本发病机制是异位EBV感染的CD 8 ^+T细胞克隆的选择性激活和扩增。因此，通过确定EBV感染的靶点和证实EBV感染细胞的克隆性，可以对EBV-HLH进行明确诊断。本研究分析了感染的CD 8 ^+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的早期诊断参数。正如预期的那样，在大多数EBV-HLH病例中，EBV感染局限于表达特定TCR Vβ的CD 8 +T细胞的单个克隆。CDR 3大小分布分析表明这些细胞是单一克隆。异常克隆表现出高水平的HLA-DR和降低水平的CD 5。因此，EB病毒感染的细胞可被鉴定为CD 8 ^+T细胞中的HLA-DR^++ CD 5 ^-细胞群。进一步的分析显示，在急性病毒感染（包括EBV）期间，在FHL 2患者中观察到类似的细胞群。

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.