PATHOGENESIS OF NEUROLOGIC LYME DISEASE
PATHOGENESIS OF NEUROLOGIC LYME DISEASE
批准号:
6346299
负责人:
BENJAMIN J LUFT
金额:
$24.29万
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
已结题
起止时间:
2000-04-01 至 2001-03-31
关键词:
Borrelia Lyme disease T lymphocyte bacterial antigens bacterial genetics central nervous system disorders cerebrospinal fluid clinical research cytokine human subject microorganism immunology neurologic manifestations pathologic process polymerase chain reaction single strand conformation polymorphism virulence
中文摘要
该项目的目标是确定疏螺旋体和特定宿主
影响中原地区入侵和持续发展的因素
神经系统(CNS)。这将通过鉴定这些菌株来完成。
嗜神经性伯氏杆菌;通过测定菌株抗原性
与神经性和持久性相关的变异;通过定义
嗜神经性、抗原变异性与早期和晚期的关系
晚期神经性莱姆综合征;通过检查宿主T细胞的作用
在疾病的传播和永久传播中的反应。
该项目将使用移行性红斑皮肤活检,脑脊液,
和莱姆病早期患者的血液样本(项目2),以及
晚期莱姆病患者的脑脊液和血液样本
(项目3)。将使用的技术包括聚合酶链式反应
(聚合酶链式反应)、单链构象多态性和细胞因子分析。
将实现以下具体目标。
具体目的1:鉴定伯氏杆菌嗜神经性菌株。
具体目标2:检验T细胞细胞因子产生的假设
(Th1 Vs Th2)对伯氏杆菌的应答,与临床相关
结果。以下预测将得到检验:
答:早期莱姆病患者表现出主要的Th2 T细胞反应,而
晚期/慢性莱姆病患者表现为主要的Th1反应。
B.Th1 T细胞反应为主的早期莱姆病患者
比早期莱姆病患者更有可能发展为慢性后遗症
占主导地位的Th2反应。这将通过相关的细胞因子进行测试
临床转归为18岁的早期莱姆病患者的生产
月份。
C.有神经系统症状的早期莱姆病患者以Th1为主
反应,而早期莱姆病患者只有一处红斑
迁徙和无全身性症状的患者以Th2反应为主。
英文摘要
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.
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