MYCOPLASMAS AND CHLAMYDIAE AND RHEUMATOID ARTHRITIS

越来越多的人认为，某些类风湿关节炎病例 (RA)和相关疾病可能源于 建立或潜伏感染后的免疫病理学应答 可能有多种微生物。这一观点的延伸是 这组疾病中的不同临床综合征 免疫调节缺陷，其表达可能受到影响， 由遗传和环境因素决定。最近的实验工作 动物对传染性病原体的易感性强烈提示 这是完全可能的此外，已知的风湿性关节炎 人类的疾病，现在有令人信服的证据表明，感染和 基因的影响发挥了作用。尽管许多人试图确定 在RA中激发感染因子，迄今为止的结果似乎是阴性的 技术伪影和解释错误目录。小心 检查这些研究中使用的实验方案， 最近在微生物学、免疫学和 分子生物学为过去的失败提供了合理的解释。所有 有迹象表明，是时候开始另一次搜索了。在 一般来说，以前的RA调查受到定义不清的影响， 疾病分类的参数和缺乏跨学科 合作滑膜炎的早期阶段，这可能提供有价值的 发病机制的线索，已收到很少的研究。的目的 目前的建议是界定那些与 近期发作的类风湿性关节炎（2 - 12个月）在充分表征的 患者人群。检测受影响的生物体的能力 关节将通过评估滑液和评估 关节镜下收集的滑膜组织目前的证据表明 两种最有可能参与慢性关节炎的药物， 人类是支原体和衣原体。因此，本研究将重点 这两种生物。将使用改进的方法分离 外周滑液和组织中的支原体和衣原体 血液单核细胞和粘膜表面。分离株进行 使用多克隆和单克隆抗体鉴定。此外，本发明还提供了一种方法， 微生物的存在将通过核酸扩增来检测 通过高灵敏度和特异性的聚合酶链反应（PCR）。PCR 还将用于确认支原体的种属鉴别， 衣原体分离株直接检测受影响的微生物 将使用免疫电子显微镜和原位 杂交方法检测对任何微生物的特异性抗体， 将使用酶联免疫吸附测定受影响的关节 结合免疫印迹的测定。患者MHC基因型也将 被确定。人口统计学和实验数据将在这样的 所有参数可以彼此相关的方式。所有数据 将在RA中获得的数据与患有骨关节炎的匹配对照进行比较。 我们建议通过结合调查来实现这些目标 具有临床流变学背景的人才， 微生物学、分子生物学、免疫学、遗传学、流行病学， 计算机技术

It has been increasingly suggested that some cases of rheumatoid arthritis (RA) and allied diseases may arise from the development of immunopathological responses following established or latent infection with a possible wide range of microorganisms. An extension of this view is that the different clinical syndromes within this group of disorders arise from immunoregulatory defects, the expression of which could be influenced by both genetic and environmental factors. Recent work in experimental animals regarding susceptibility to infectious agents strongly suggest that this is entirely possible. Furthermore, there are known rheumatic diseases of man for which there is now cogent evidence that infection and genetic influence play a role. Despite many attempts to identify the inciting infectious agent(s)in RA, results to date seem to be a negative catalogue of technical artifact and interpretative error. Careful examination of experimental protocols used in these studies coupled with recent conceptual and technical advances in microbiology, immunology and molecular biology provide plausible explanations of past failure. All indications are that the time has come to initiate another search. In general, previous investigations of RA have suffered from ill-defined parameters for disease classification and lack of interdisciplinary cooperation. The early stages of synovitis, which may provide valuable clues to pathogenesis, have received little study. The purpose of the present proposal is to define those infectious agents associated with rheumatoid arthritis of recent onset (2 to 12 mos.) in well characterized patient populations. The ability to detect organisms within affected joints will be enhanced by evaluation of synovial fluid and by evaluation of synovial tissue collected by arthroscopy. Current evidence suggests that two of the most likely agents to be involved in chronic arthritis in humans are mycoplasmas and chlamydiae. Thus, the present study will focus on these two organisms. Improved methods will be used for isolation of mycoplasmas and chlamydiae from synovial fluid and tissue, peripheral blood monocytes, and when indicated mucosal surfaces. Isolates will be identified using polyclonal and monoclonal antibodies. In addition, presence of microorganisms will be detected by amplication of nucleic acid by the highly sensitive and specific polymerase chain reaction (PCR). PCR will also be used to confirm species identity of mycoplasmal and chlamydial isolates. Detection of microorganisms directly in affected joints will be verified using immunoelectron microscopy and in situ hybridization. Detection of specific antibody to any organism detected in affected joints will be determined using enzyme-linked immunosorbent assays in conjunction with immunoblotting. Patient MHC genotypes will also be determined. Demographic and experimental data will be collected in such a way that all parameters may be correlated one with the other. All data obtained in RA will be compared to matched controls with osteoarthritis. We propose to accomplish these objectives by combining the investigative talents of individuals with backgrounds in clinical rheumatology, microbiology, molecular biology, immunology, genetics, epidemiology, and computer technology.