Pathogenesis and Prognosis of Skin Diseases Caused by Host Immune Responses against EB virus Latent Infections

1) EB病毒（EBV）相关NK/ t细胞谱。淋巴增殖性疾病（LPD）：我们以eb病毒相关的LPD病例为回顾中心，明确了疾病谱系和预后（Arch Dermatol 2006, Eur J Dermatol 2006）。我们建立了皮肤淋巴瘤的网站登记系统，并开始收集流行病学资料。2)无创诊断方法基因表达分析：建立了利用结皮检测潜伏感染EBV及其细胞基因产物的无创方法（专利号PCT/JP2006/317851）。该方法可用于其他疱疹病毒感染和细胞基因表达的分析。3) eb病毒在皮肤军团中再激活的证据，以及潜伏模式的改变：严重疾病患者在皮肤病变中表达了再激活信号（BZLF-1 mRNA），而轻度疾病患者则没有。然而，在轻度疾病中，LMP-1的表达水平比外周血中的表达水平升高。4) ebv感染细胞系细胞分析：对建立的细胞系进行细胞学分析。PMA和某些细胞因子成功诱导ebv感染的再激活。具有潜伏感染周期的NK/ t细胞克隆。5)宿主免疫反应：我们发现宿主ea的致病意义，对各种EBV基因产物的反应在皮肤病变的发展中至关重要。6)治疗方法：分析C/T抗原引起的宿主免疫反应（国际癌症杂志，2007）。在同一模型中研究了免疫入侵机制（Cancer Immunol Immunother 2006）。我们发现一些ebv感染的细胞对HDAC抑制剂敏感。这些观察结果可能为ebv相关LPD的免疫药理学治疗提供有价值的数据。7)我们已经淹没了包括ebv相关LPD在内的皮肤淋巴瘤指南的版本。

1) The spectrum of EB virus (EBV)-associated NK/T-cell. lymphoproliferative disorders (LPD): We have registered cases with EBV-asscciated LPD as a reviewing center, and clarified the disease spectrum and the prognoses (Arch Dermatol 2006, Eur J Dermatol 2006). We have established a website registration system for cutaneous lymphomas, and began to collect the epidemiological data.2) Gene expression analysis using a noninvasive diagnostic method: We have established a noninvasive method using crusts for detection of latently infected EBV and cellular gene products (PATENT PCT/JP2006/317851). This method is available for analysis of other herpesvirus infections and cellular gene expression.3) Evidence for EBV reactivation in the skin legions, and alteration of latency patterns: Patients with severe diseases expressed a reactivation signal (BZLF-1 mRNA) in the skin lesions, while patients with mild diseases did not. In the mild disgase, however, LMP-1 expression levels were increased as compared with those in peripheral blood. 4) Analysis of EBV-infected cell line cells: We performed cytological analysis on the established cell lines. PMA and certain cytokines successfully induced reactivation in EBV-infected.NK/T-cell clones with a latent-infection cycle.5) Host immune responses: We found that pathogenic significance of host ea, responses against various EBV gene products was essential in the development of the skin lesions.6) Therapeutic approach: Host immune responses evoked to C/T antigens were analysed (Int J Cancer 2007). Immune ivasion mechanisms were studied in the same model (Cancer Immunol Immunother 2006). We found that some EBV-infected cells were sensitive to HDAC inhibitors. These observations may provide valuable data for immunopharmacological treatments for EBV-related LPD.7) We have drown out the version of guideline for cutaneous lymphomas including EBV-associaiated LPD.