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: 6133360
• 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/6133360
• 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（MS）是中枢神经系统（CNS）的炎性脱髓鞘疾病。虽然MS的病因尚不清楚，但有相当多的间接证据表明感染因子在疾病发展中的作用。虽然仍然强烈考虑病毒剂，但在MS患者中使病毒缺陷的努力已经失败。我们提出的初步数据表明，衣原体可能是MS的一个候选病原体。这一推断是基于：a）存在的PCR产物的主要外膜蛋白（MOMP）基因的衣原体;在患有继发性进行性MS的患者的脑脊液（CSF）中存在肺炎衣原体抗体，但在其他神经系统疾病对照（OND）中不存在; B）存在抗肺炎衣原体抗体。肺炎抗原;和c）死于MS的患者的脑尸检样品中衣原体抗原的存在。肺炎杆菌属于感染人类和其它脊椎动物的细胞内病原体属。C.肺炎与许多慢性疾病有关，包括那些被认为是自身免疫性的疾病。衣原体在人类和其他脊椎动物中引起慢性持续性炎症，并且在所有情况下组织损伤似乎是免疫介导的。免疫激活C。肺炎链球菌感染包括诱导T细胞对热休克蛋白的应答和产生促炎细胞因子。我们的建议满足了将C.肺炎和多发性硬化症。这些包括直接通过培养或通过证明C的存在来检测生物体的能力。肺炎克雷伯氏菌DNA和mRNA以及胞浆内或生物体的证据，如通过MS患者的CNS组织中的电子显微镜所证明的。CNS隔室中所含的肺炎链球菌感染将构成微生物感染的强有力的间接证据。