A STUDY ON PATHOGENESIS AND PROGNOSIS OF EPSTEIN-BARR VIRUS-ASSOCIATED CUTANEOUS LYMPHOPROLIFERATIVE DISORDERS

潜伏eb病毒感染与多种恶性疾病有关，包括非洲伯基特淋巴瘤、鼻咽癌、移植后淋巴细胞增生性疾病、自然杀伤细胞(NK)/ t细胞淋巴瘤、慢性活动性eb病毒感染、胃癌、脓胸相关淋巴瘤和平滑肌肿瘤。最近，在亚洲、墨西哥和秘鲁，发现有特殊的hiv样爆发的患者进展为ebv相关的恶性淋巴瘤。我们的研究表明，典型和严重的HV都包括在ebv感染的T细胞介导的皮肤疾病的范围内，严重的HV组可能有明显的ebv相关的NK/T细胞淋巴增生性疾病，包括对蚊虫叮咬的过敏、慢性活动性EB病毒感染、噬血细胞淋巴组织细胞病和NK/T细胞淋巴瘤，这些疾病的结果往往是致命的。的发展和恶化严重HV-like病变可能发生地方性地由于影响 ... 更多的患者的遗传背景,巴尔病毒亚型,免疫学宽容EBV感染,或环境因素。在同一患者身上建立了感染EB病毒的不同T、NK细胞系，在疫苗形水疱和蚊虫叮咬的皮损处浸润了不同类型的细胞。这些观察结果表明，患者血液中含有EB病毒感染的T、NK和B细胞池，这可能解释了与潜伏EB病毒感染相关的临床症状的多样性。在皮肤病变中，我们可以发现细胞毒性t细胞的参与和EBV再激活的线索。某些触发因素，如蚊虫叮咬和紫外线暴露，可诱导EBV重新激活，进而引起继发性全身症状。在与高知大学的今井教授的合作中，我们已经证明，突变型EBNA1可以作为一个显性负效应者，有效地阻碍ebv依赖性恶性表型的细胞，而不管病毒潜伏期或组织起源如何。这种突变体将提供一种额外的治疗策略，专门针对ebv相关的恶性肿瘤。为了诊断目的，我们建立了一种实时PCR方法来测定EBV DNA载量，并建立了一种新的无创方法来检测皮肤痂中潜伏的EBV感染（专利：2005-961917，冈山大学）。我们相信，这些技术进步有助于早期诊断和监测疾病进展。少

Latent EBV infection has been implicated in a variety of malignant conditions, including African Burkitt's lymphoma, nasopharyngeal carcinoma, post-transplantation lymphoproliferative disorders, natural killer (NK)/T-cell lymphomas, chronic active EBV infection, gastric cancer, pyothorax-associated lymphoma, and smooth-muscle tumors. Recently, patients in Asia, Mexico, and Peru with peculiar HV-like eruptions were found to progress to EBV-associated malignant lymphoma. Our study has clarified that both typical and severe HV are included within the spectrum of cutaneous disorders mediated by EBV-infected T cells, and the severe HV group may have overt EBV-associated NK/T cell lymphoproliferative disorders including hypersensitivity to mosquito bites, chronic active EB virus infection, hemophagocytic lymphohistiocytosis and NK/T cell lymphomas with a frequently fatal outcome. The development of and the progression to the severe HV-like lesions might occur endemically due to the influence … More s of the patient's genetic background, EBV subtypes, immunological tolerance to EBV infection, or environmental factors.Different T or NK cell lines infected with EB virus were established from the same patient, and different cell types were infiltrated in cutaneous lesions of hydroa vacciniforme and mosquito bites. These observations have demonstrated that the patients'blood contains a pool of EB virus-infected T, NK and B cells, which may explain a diversity of clinical symptoms related to latent EB virus infection. In the cutaneous lesions, we could find the involvement of cytotoxic T-cells and the clues of reactivation of EBV. A certain trigger such as mosquito bites and ultraviolet exposure may induce reactivation of EBV, which may in turn evoke secondary systemic symptoms.In collaboration with Prof.S.Imai (Kochi Univ.), we have demonstrated that mutant EBNA1 can act as a dominant-negative effector that efficiently impedes the EBV-dependent malignant phenotypes in cells regardless of viral latency or tissue origin. This mutant will afford an additional therapeutic strategy specifically targeting EBV-associated malignancies.For diagnostic purpose, we have established a real-time PCR method to determine the EBV DNA load, and a novel, noninvasive method to detect latent EBV infection in the skin crusts (PATENT : 2005-961917, Okayama Univ.). We believe that these technical advances contribute to the early diagnosis and the monitoring of the disease progression. Less