AUTOIMMUNE ROLE IN AIDS DEMENTIA COMPLEX

感染人类免疫缺陷病毒(HIV)通常 牵涉到中枢神经系统。最频繁的 感染艾滋病毒引起的神经精神综合征是一种 衰弱进行性肌无力复合体(ADC)。这个 ADC的发病机制尚不清楚，但似乎是由于 未明确的二次病毒效应，而不是直接细胞 感染。基于我们积极的初步数据- 免疫印迹和免疫印迹法检测特异性抗脑抗体 间接免疫荧光--这项提议将探索其作用 ADC中针对脑组件的自身抗体(AutoAbs)。 样本将从现有的样本库中进行检查 从ADC患者和对照组收集：血清(n大于 1000)，配对的脑脊液和血清(n=100)，以及脑+配对的脑脊液和 血清50例。正在进行的标本收集工作将继续从 接受正式神经心理学评估的患者 和神经学治疗方案。将包括广泛的控制措施。 脑脊液和血清将进行全脑自身抗体检测， 特异性脑抗原(包括髓鞘碱性蛋白， 神经节苷脂、n-钙调素、半乳脑苷脂)和细胞干细胞 (包括神经元和神经胶质线)。既有西方人的技艺 免疫印迹和间接免疫荧光将用于 在考试之前。免疫组织化学将被用来观察 用于原位脑自身抗体。此外，免疫复合体(IC) 我们在ADC患者的脑脊液中检测到 分离，并检查IC组件的大脑反应性 以及艾滋病毒成分。IC将使用3种分析方法进行测量 (Raji细胞，固相CLG，聚乙二醇单抗夹心法)，Raji分离 细胞洗脱或聚乙二醇沉淀法。数据将使用以下工具进行分析 适当的统计方法。这项建议应该会有所帮助 确定自身免疫进程是否链接到ADC。它 也应该更广泛地为关于 病毒和自身免疫紊乱在疾病中的潜在作用 精神错乱和神经精神疾病。

Infection with the human immunodeficiency virus (HIV) commonly involves the central nervous system. The most frequent neuropsychiatric syndrome due to infection with HIV is a debilitating progressive demintia complex (ADC). The pathogenesis of ADC is not known, but appears to be due to undefined secondary viral effects rather than direct cell infection. Based on our positive preliminary data-the demonstration of specific antibrain antibody on Western blots and indirect immunofluorescence- this proposal will explore the role of autoantibodies (autoAbs) to brain components in ADC. Specimens will be examined from existing banks of samples collected from ADC patients and controls: sera (n greater than 1000), paired CSF and sera (n=100),and brain plus paired CSF and sera (n=50). Ongoing collection of specimens will continue from patients who are being evaluated by formal neuropsychological and neurologic protocols. Extensive controls will be included. CSF and serum will be examined for autoAb to whole brain, specific brain antigens (including myelin basic protein, gangliosides, n-CAM, galactocerebroside) and cell lystes (including neuronal and glial lines). Both the technique of Western immunoblots and indirect immunofluorescene will be used for the above examination. Immunohistochemistry will be used to look for in-situ brain autoAb. In addition, the immune complexes (IC) we detect in the CSF from ADC patients will be isolated and dissociated, and the IC components examined for brain reactivity as well as HIV components. IC will be measured using 3 assays (Raji cell, solid phase Clg, and PEG-ELISA) and isolated by Raji cell elution or PEG precipitation. Data will be analyzed using appropriate statistical methods. The proposal should help determine whether an autoimmune process is linked to ADC. It should also contribute more broadly to information on the potential role of viruses and autoimmune disturbances in dementing and neuropsychiatric diseases.