MYCOPLASMAS AND CHLAMYDIAE AND RHEUMATOID ARTHRITIS

越来越多的人认为一些类风湿性关节炎的病例 (RA)和相关疾病可能因以下发展而出现 既往感染或潜伏感染后的免疫病理反应 可能存在广泛的微生物。此视图的扩展为 在这组疾病中出现了不同的临床症状 来自免疫调节缺陷，其表达可能受到影响 由遗传和环境因素共同决定。最新的实验工作 动物对感染性物质的易感性强烈建议 这是完全可能的。此外，还有已知的风湿病 人类的疾病，现在有令人信服的证据表明感染和 基因影响起到了一定的作用。尽管多次尝试确定 煽动感染因子(S)在RA中，迄今结果似乎为阴性 技术遗迹和解释错误目录。小心 检查这些研究中使用的实验方案，并结合 微生物学、免疫学和生物医学领域的最新概念和技术进展 分子生物学为过去的失败提供了看似合理的解释。全 有迹象表明，发起另一次搜索的时机已经到来。在……里面 将军，之前对RA的调查都是定义不清的 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，得到的研究很少。该计划的目的是 目前的建议是定义与以下各项有关的传染病病原体 新近发病的类风湿性关节炎(2-12个月)在很好的特点中 患者群体。检测受影响的生物体的能力 关节将通过滑液的评估和评估得到加强 关节镜下收集的滑膜组织。目前的证据表明 两种最有可能与慢性关节炎有关的病原体 人类是支原体和衣原体。因此，本研究将集中于 在这两种生物上。将使用改进的方法分离出 外周滑液和组织中的支原体和衣原体 外周血单核细胞，如有提示，可见粘膜表面。分离株将是 用多克隆抗体和单抗进行鉴定。此外, 微生物的存在将通过核酸的扩增来检测 通过高度敏感和特异的聚合酶链式反应(PCR)。聚合酶链反应 还将用于确认支原体和支原体的物种鉴定 衣原体分离株。直接检测受影响地区的微生物 关节将使用免疫电子显微镜和原位进行验证。 杂交。对检测到的任何生物的特定抗体的检测 将使用酶联免疫吸附剂确定受影响的关节 检测与免疫印迹相结合。患者的MHC基因也会 要下定决心。人口学和实验数据将收集在这样的 所有参数可以相互关联的一种方式。所有数据 在RA中获得的结果将与患有骨关节炎的匹配对照组进行比较。 我们建议通过将调查与调查相结合来实现这些目标 具有临床风湿病专业背景的人才， 微生物学、分子生物学、免疫学、遗传学、流行病学和 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.