ANALYSIS OF ASSOCIATION BETWEEN C. PNEUMONIAE AND MS

肺炎衣原体与多发性硬化症之间的关联性分析

• 批准号: 6539979
• 负责人: SUBRAMANIAM SRIRAM
• 金额: $ 18.9万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6539979
• 关键词: Chlamydiaceae; T lymphocyte; antibacterial antibody; antigen antibody reaction; bacteria infection mechanism; bacterial antigens; bacterial pneumonia; bacterial proteins; biopsy; central nervous system disorders; cerebrospinal fluid; clinical research; electron microscopy; human subject; immunoregulation; inflammation; membrane proteins; multiple sclerosis; myelin; myelinopathy; oligodendroglia; pathologic process; polymerase chain reaction; tissue /cell culture; western blottings

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). Although the etiology of MS is not known, there is considerable indirect evidence to suggest the role of infectious agents in the development of the disease. While a viral agent is still strongly considered, efforts to defect a virus in patients with MS have failed. We present preliminary data which argue that Chlamydiae Pneumoniae may be a candidate pathogen in MS. This inference is based on: a) the presence of PCR products to major outer membrane protein (MOMP) gene of C. pneumoniae in the cerebrospinal fluid (CSF) of patients with secondary progressive MS but not in other neurologic disease controls (OND); b) the presence of antibody to C. pneumonia antigens in the CSF of MS patients; and c) the presence of chlamydial antigens in brain autopsy specimens of patients who have died of MS. C. pneumoniae belongs to a genus of intracellular pathogens that are infectious to humans and other vertebrates. C. pneumoniae are implicated in many chronic diseases, including those presumed to be autoimmune. Chlamydiae cause chronic persistent inflammation in humans and other vertebrate animals and tissue injury in all cases appears to be immune mediated. Immune activation by C. pneumoniae includes induction of T cell response to heat shock proteins and production of pro-inflammatory cytokines. Our proposal sets out to meet the necessary criteria required to attribute a causal association between C. pneumoniae and MS. These would include the ability to detect the organism either directly by culture or by demonstrating the presence of C. pneumoniae DNA and mRNA and evidence of intracytoplasmic or organisms as proven by electron microscopy in the CNS tissue of patients with MS. Also, the presence of an immune response to C. pneumoniae that is contained within the CNS compartment will constitute strong circumstantial evidence of microbial infection.

多发性硬化症(MS)是一种中枢神经系统(CNS)炎症性脱髓鞘疾病。虽然多发性硬化症的病因尚不清楚，但有相当多的间接证据表明感染性病原体在该病的发展中所起的作用。虽然病毒制剂仍被强烈考虑，但使多发性硬化症患者的病毒缺陷的努力失败了。我们提供的初步数据表明肺炎衣原体可能是MS的候选病原体。这一推断基于：a)继发性进展性MS患者的脑脊液(CSF)中存在肺炎衣原体主要外膜蛋白(MOMP)基因的聚合酶链式反应产物，而其他神经系统疾病对照(OND)患者脑脊液中不存在；b)MS患者的脑脊液中存在肺炎衣原体抗体；以及c)肺炎衣原体死亡患者的脑尸检标本中存在衣原体抗原，属于一种可感染人类和其他脊椎动物的细胞内病原体。肺炎衣原体与许多慢性疾病有关，包括那些被认为是自身免疫性疾病的疾病。衣原体在人类和其他脊椎动物中引起慢性持续性炎症，所有病例的组织损伤似乎都是由免疫调节的。肺炎衣原体的免疫激活包括诱导T细胞对热休克蛋白的反应和产生促炎细胞因子。我们的提案提出了满足确定肺炎衣原体与MS之间因果联系所需的必要标准，这些标准将包括直接通过培养或通过证明肺炎衣原体DNA和mRNA的存在以及电子显微镜证明MS患者的中枢神经系统组织中存在细胞质内或生物体的证据来检测该生物体的能力。此外，对肺炎衣原体的免疫反应的存在将构成微生物感染的强有力的间接证据。

项目成果

Detection of chlamydial bodies and antigens in the central nervous system of patients with multiple sclerosis.

多发性硬化症患者中枢神经系统衣原体和抗原的检测。

• DOI: 10.1086/431518
• 发表时间: 2005
• 期刊: The Journal of infectious diseases.
• 作者: Sriram,Subramaniam;Ljunggren-Rose,Asa;Yao,Song-Yi;WhetsellJr,WilliamO
• 通讯作者: WhetsellJr,WilliamO