CHLAMYDIA AND THE PATHOGENESIS OF REITER'S SYNDROME

长期以来，雷特综合征(RS)的一种传染病病原学 怀疑，因为这种疾病通常是在发作后观察到的 尿道炎或痢疾。尽管许多细菌物种可以 与这种疾病有关的沙眼衣原体已经成为一种 RS的主要病原体，主要是由于其在 人口。尽管这种有机体是主要的性传播途径 细菌在工业化世界中，自然界的许多方面 这类感染的历史仍然相对较少被了解；例如，两者都 衣原体感染的流行病学和临床特征提示 在某些情况下，有机体可以持续处于培养阴性状态 情况。该实验室最近的工作直接提供了 持久性/隐匿性衣原体的分子生物学证据 所有解剖相关部位的感染；即，我们证明了 通过一种简单的方法可以证明衣原体核酸水平很高 分子杂交筛选及聚合酶链式反应 (聚合酶链式反应)分析，在沙眼患者的结膜样本和 在标准的尿路和宫颈拭子中，都是衣原体- 标准培养或基于抗体的筛查试验均为阴性。 重要的是，我们还证明了培养阴性的滑膜组织 RS患者体内同样含有高水平的衣原体RNA和DNA， 而来自其他关节疾病患者的平行样本则没有。 此外，初步证据表明， 杂交或聚合酶链式反应分析都是从活的， 新陈代谢活性衣原体。在本申请中，我们描述了研究 评估隐形眼病的患病率和临床后果 合并/不合并RS患者滑膜衣原体感染的研究在……里面 这些和相关的实验室研究，我们解决临床，生化， 和分子生物学问题有关的意义，自然 历史、特点、发病机制及抗生素 这种隐蔽的衣原体感染的易感性。我们进一步 建议进行详细的分子遗传学研究，以定义转录 和隐匿性衣原体的总代谢活性 细胞，我们描述了研究一种可能的机制的实验 用于隐匿性滑膜衣原体感染的复活。这些 研究将为开发有效的治疗方法提供新的见解 针对RS患者的计划，它们将增强我们对 衣原体的重要但尚未被认识的方面 发病过程。

An infectious etiology for Reiter's syndrome (RS) has long been suspected, since this disease has often been observed to follow episodes of urethritis or dysentery. Although many bacterial species can be associated with the disease, Chlamydia trachomatis has emerged as a primary etiologic agent in RS, due largely to its prevalence in the population. Although this organism is the major sexually-transmitted bacterium in the industrialized world, many aspects of the natural history of such infections remain relatively poorly understood; eg, both epidemiological and clinical features of chlamydial infections suggest that the organism can persist in a culture-negative state under some circumstances. Recent work from this laboratory has provided direct molecular biological evidence for persistent/inapparent chlamydial infections in all anatomically relevant sites; ie, we demonstrated that high levels of chlamydial nucleic acids can be demonstrated, via a simple molecular hybridization screening assay and by polymerase chain reaction (PCR)-based analysis, in conjunctival samples from trachoma patients and in standard urethral and cervical swabs, all of which are chlamydia- negative by standard culture or antibody-based screening assays. Importantly, we also demonstrated that culture-negative synovial tissues from RS patients similarly contain high levels of chlamydial RNA and DNA, while parallel samples from patients with other arthropathies do not. Further, preliminary evidence indicates that the nucleic acids shown in either hybridization or PCR assays are derived from viable, metabolically-active chlamydia. In this application, we describe studies to assess the prevalence and clinical consequences of inapparent chlamydial infection of the synovium in patients with/without RS. In these and related laboratory studies, we address clinical, biochemical, and molecular biological questions regarding the significance, natural history, characteristics, mechanisms of pathogenesis, and antibiotic susceptibility of such inapparent chlamydial infections. We further propose detailed molecular genetic studies to define the transcriptional and overall metabolic activity of inapparently-infecting chlamydial cells, and we describe experiments to investigate one possible mechanism for the reactivation of inapparent synovial chlamydial infection. These studies will give new insights for development of effective treatment programs for RS patients, and they will augment our understanding of an important but as yet poorly recognized facet of the chlamydial pathogenesis process.