PATHOGENESIS OF NEUROLOGIC LYME DISEASE

该项目的目标是确定疏螺旋体和宿主特异性 在中央的入侵和持久性的因素 神经系统（CNS）。这将通过鉴定这些B菌株来完成。 嗜神经性的伯氏菌;通过测定菌株抗原性 与嗜神经性和持久性相关的变异;通过定义 嗜神经性、抗原变异性和早期 晚期神经性莱姆病综合征;并通过检查宿主T细胞的作用， 疾病传播和延续的反应。 本项目将使用游走性红斑皮肤活检，脑脊液， 和早期莱姆病患者的血液样本（项目2），以及 晚期莱姆病患者的脑脊液和血液样本 （项目3）。使用的技术包括聚合酶链反应 (PCR)单链构象多态性和细胞因子测定。 将处理以下具体目标。 具体目标1：鉴定B的嗜神经性菌株。burgdorferi。 具体目的2：检验T细胞细胞因子产生 (Th1 vs Th 2）对B. burgdorferi，与临床 结果。将检验以下预测： A.早期莱姆病患者表现出主要的Th 2 T细胞应答，而 晚期/慢性莱姆病患者显示出主要的Th 1应答。 B。Th 1 T细胞应答占优势的早期莱姆病患者 可能比早期莱姆病患者发展慢性后遗症， Th 2反应占主导地位。这将通过将细胞因子 早期莱姆病患者在18岁时的临床结局 个月 C.有神经系统症状的早期莱姆病患者Th 1细胞占优势， 反应，而早期莱姆病患者的单一病变的红斑 无全身症状的移行者具有主要的Th 2应答。

The goal of this project is to identify Borrelial and host-specific factors involved in the invasion of and persistence within the central nervous system (CNS). This will be done by identifying those strains of B. burgdorferi which are neurotropic; by determining strain antigenic variation associated with neurotropism and persistence; by defining the relationship between neurotropism ,antigenic variability, and early and late neurologic Lyme syndromes; and by examining the role of host T-cell responses in dissemination and perpetuation-of disease. This project will use erythema migrans skin biopsy, cerebrospinal fluid, and blood samples from early Lyme disease patients (Project 2), and cerebrospinal fluid and blood samples from late Lyme disease patients (Project 3). Techniques to be used include polymerase chain reaction (PCR), single-stranded conformational polymorphism and cytokine assays. The following specific aims will be addressed. Specific Aim 1: To identify neurotropic strains of B. burgdorferi. Specific Aim 2: To test the hypothesis that T-cell cytokine production (Th1 vs Th2) in response to B. burgdorferi, correlates with clinical outcome. The following predictions will be tested: A. Early Lyme patients show a predominant Th2 T-cell response, while late/chronic Lyme patients show a predominant Th1 response. B. Early Lyme patients with a predominant Th1 T-cell response are more likely to develop chronic sequelae than early Lyme disease patients with a predominant Th2 response. This will be tested by correlating cytokine production of early Lyme disease patients with clinical outcome at 18 months. C. Early Lyme patients with neurologic symptoms have a predominant Th1 response, while early Lyme patients with a single lesion of erythema migrans and no systemic symptoms have a predominant Th2 response.