CHRONIC EPSTEIN BARR VIRUS INFECTION AND CHRONIC FATIGUE SYNDROME

这个项目的目标是描述严重的慢性感染的特征。 患有EB病毒(EBV)和其他淋巴增生性疾病。和 为了阐明慢性疲劳综合征的多个方面， 早些时候，被认为与EBV感染有关。到目前为止的这项研究 该项目已涉及约250名患者。包括7名患者，他们 根据临床诊断为严重的慢性EBV感染， 组织学、分子学和血清学特征。我们将继续检查 重度慢性EB病毒相关性患者的免疫学特征 淋巴增殖和探索治疗方法。阿昔洛韦、阿尔法和伽马 干扰素被证明没有什么价值，但免疫抑制疗法是 长期使用效果良好。 详细的免疫学、神经学、内分泌学和心理学研究 正在对选定的慢性疲劳症患者进行研究。到目前为止， 我们仍然没有发现一致的实验室异常情况 然而，我们一直在寻求慢性疲劳综合症的诊断 群体异常在神经精神、免疫方面的基础和意义 和内分泌系统。关于垂体-肾上腺的一系列研究 促肾上腺皮质激素释放激素和促肾上腺皮质激素的反应性 脊髓液中神经肽和儿茶酚水平提示中枢神经系统缺陷 CRH释放。由于CRH诱导中枢神经系统唤醒，这些神经内分泌发现 提示慢性疲劳综合征嗜睡的新机制 病人可能会被解释。我们正在以一种新的方式进行这些观察 一系列研究和新的患者队列。精氨酸加压素 24名患者和20名对照组接受了输液，以刺激和 测试HPA轴。结果将在94财年晚些时候公布。四十岁- 5名患者已经参加了一项安慰剂对照试验 氢化可的松治疗。它应该允许我们检验这样的假设 皮质类固醇缺乏会导致症状。我们还认识到离散的 慢性疲劳综合征患者淋巴细胞表型和体外培养的异常 对有丝分裂原的反应模式暗示着温和的免疫激活。 幼稚(CD4xCD45RA)T细胞减少，而 记忆性(CD4XCD45RO)T细胞，带有黏附标记(LFA3、CD29等)。 我们已经开始在其他几项实验室研究中继续研究这些发现 涉及来自患者和对照的纯化细胞群，以及 患有急性流感的患者。一种强有力的多学科方法来 综合症仍在继续。

The goals of this project are to characterize severe chronic infections with Epstein Barr Virus (EBV) and other lymphoproliferative disorders. and to elucidate multiple aspects of the chronic fatigue syndrome which was, earlier, considered to be related to EBV infection. To date this research project has involved about 250 patients. Included are 7 patients who were diagnosed with severe chronic EBV infections on the basis of clinical, histological, molecular and serologic features. We continue to examine immunologic features of patients with severe chronic EBV-associated lymphoproliferation and explore treatments. Acyclovir, alpha and gamma interferons proved of little value, but immunosuppressive therapies are being used with good long-term results. Detailed immunologic, neurologic, endocrinologic and psychologic studies are being conducted on selected patients with chronic fatigue. To date, we still have no consistent laboratory abnormality that permits a clear diagnosis of the chronic fatigue syndrome, however, we have been pursuing the basis and meaning of group abnormalities in neuropsychiatric, immune and endocrine systems. A series of studies of the pituitary-adrenal responsiveness to corticotropin releasing hormone and ACTH and of neuropeptide and catechol levels in spinal fluid suggest deficient central CRH release. Since CRH induces CNS arousal, these neuroendocrine findings suggest a new mechanism whereby the lethargy of chronic Fatigue Syndrome patients may be explained. We are pursuing these observations in a new series of studies and a fresh patient cohort. Arginine-Vasopressin infusions have been given to 24 patients and 20 controls to stimulate and test the HPA axis. The results will be available in late FY94. Forty- five patients were enrolled already in a placebo-controlled trial of hydrocortisone treatment. It should permit us to test the hypothesis that corticosteroid deficit leads to symptoms. We also recognized discrete abnormalities in CFS patient lymphocyte phenotype and in vitro responsiveness to mitogens in patterns suggesting mild immune activation. There is a reduction in naive (CD4xCD45RA) t Cells and an increase in memory (CD4XCD45RO) T cell bearing adhesion markers (LFA3, CD29, etc.). We have begun to pursue these findings in several other laboratory studies involving purified cell populations from patients and controls and in patients with acute influenza. A vigorous, multidisciplinary approach to the syndrome continues.