AUTOIMMUNE ROLE IN AIDS DEMENTIA COMPLEX

感染人类免疫缺陷病毒（HIV）通常 涉及中枢神经系统。 最常见的 HIV感染引起的神经精神综合征是一种 使人衰弱的进行性痴呆综合征（ADC）。 的 ADC的发病机制尚不清楚，但似乎是由于 不确定的继发性病毒效应，而不是直接细胞 感染 根据我们积极的初步数据， 在蛋白质印迹上显示特异性抗脑抗体， 间接免疫荧光-这项建议将探讨的作用， 自身抗体（autoAb）的ADC中的脑成分。 将从现有的样本库中检查样本 从ADC患者和对照收集：血清（n大于 1000）、配对CSF和血清（n = 100）以及脑+配对CSF和血清（n = 100）。 血清（n = 50）。 正在进行的标本采集将从 正在接受正式神经心理学评估的患者 和神经学协议 将包括广泛的控制。 将检查CSF和血清中的全脑自身抗体， 特异性脑抗原（包括髓鞘碱性蛋白， 神经节苷脂、n-CAM、半乳糖苷脂）和细胞溶解 （包括神经元和神经胶质细胞系）。 西方的技术 免疫印迹和间接免疫荧光将用于 高于考试。 免疫组织化学将被用来寻找 用于原位脑自体抗体。 此外，免疫复合物（IC） 我们在ADC患者的CSF中检测到的抗体将被分离， 分离，并检查IC组件的脑反应性 以及艾滋病毒成分。 将使用3种测定方法测量IC (Raji细胞、固相Clg和PEG-ELISA），并由Raji分离 细胞洗脱或PEG沉淀。 将使用以下方法分析数据： 适当的统计方法。 该提案应有助于 确定自身免疫过程是否与ADC相关。 它 还应更广泛地宣传 病毒和自身免疫紊乱在 痴呆和神经精神疾病。

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.