SLE ANTIBODIES TO NEURONS AND LYMPHOCYTES: PATHOBIOLOGY

中枢神经系统功能障碍是系统性狼疮的常见现象 红斑，是严重危及生命的表现之一 疾病。 免疫复合物介导的血管炎，机制 在大多数器官系统中负责组织损伤，很少在 CNS疾病患者的大脑。 这方面的一项主要研究成果是 实验室一直在调查抗体反应的作用 与人脑神经元细胞在狼疮发病机制中的作用 神经精神症状 我们的研究表明， 狼疮患者具有与人类神经元反应的循环抗体，并且 这些抗体中的许多与人类上的抗原交叉反应 淋巴细胞 这些抗体的致病作用是由 中枢神经系统内抗神经元抗体的密切联系 系统和活动性CNS狼疮。 在本申请中，我们提出了更多 详细分析神经元的致病潜力， 淋巴细胞反应性抗体 我们的目标是了解这些 抗体进入神经系统， 他们的反应。 我们将确定抗体是否在当地产生 中枢神经系统内，或者如果它们从血清通过 血脑屏障的渗漏 我们将研究它们的反应， 调节大脑功能的神经递质受体， 利用神经元和淋巴细胞反应性抗体， 表征这两种细胞类型共有的抗原，并分析它们的 淋巴细胞亚群分布作为潜在的探针 免疫调节改变和神经系统功能障碍之间的联系， 描述SLE的特征。

Central nervous system dysfunction is a common occurrence in systemic lupus erythematosus, and it is one of the serious life-threatening manifestations of the disease. Immune complex-mediated vasculitis, the mechanism responsible for tissue damage in most organ systems, is rarely found in the brain of patients with CNS disease. A major research effort in this laboratory has been the investigation of the role of antibodies reactive with neuronal cells from human brain in the pathogenesis of lupus neuropsychiatric manifestations. Our studies have demonstrated that most lupus patients have circulating antibodies reactive with human neurons, and many of those antibodies are cross-reactive with antigens on human lymphocytes. A pathogenetic role for those antibodies is suggested by the close association of antineuronal antibody within the central nervous system and active CNS lupus. In this application we are proposing more detailed analysis of the disease-producing potential of the neuron and lymphocyte reactive antibodies. Our aims are to understand how these antibodies get into the nervous system and to define the antigens with which they react. We will determine if the antibodies are produced locally within the central nervous system or if they enter from the serum through a leak in the blood-brain barrier. We will investigate their reactivity with the neurotransmitter receptors that regulate brain function, and we will utilize the neuron and lymphocyte reactive antibodies to physically characterize the antigens shared by those two cell types and analyze their distribution on lymphocyte subpopulations as a probe into the potential link between altered immune regulation and nervous system dysfunction that characterize SLE.