The Role of Mycobacteria in Crohn's Disease

分枝杆菌在克罗恩病中的作用

• 批准号: 6622766
• 负责人: DAVID Y GRAHAM
• 金额: $ 22.58万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6622766
• 关键词: Crohn's disease; Mycobacterium; antibiotics; bacterial disease; clinical research; diagnosis design /evaluation; disease /disorder etiology; gastrointestinal disorder chemotherapy; gastrointestinal infection; human subject; human therapy evaluation; in situ hybridization; patient oriented research; polymerase chain reaction; serology /serodiagnosis

DESCRIPTION (provided by applicant): Crohn's disease is an idiopathic non- caseating granulomatous disease. One of the proposed etiologies is infection with Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis), the causative agent of Crohn's-like disease in ruminants (Johne's disease). Recent evidences to support M paratuberculosis infection in Crohn's disease include: 1) its isolation from Crohn's disease tissues and breast milk by culture, 2) its identification in tissues by PCR assays, 3) its detection as cell wall deficient forms in tissues by in situ hybridization, 4) the long term remission (possibly cure) in an increasing number of Crohn's patients by using anti-mycobacterial therapies, and 5) by an association with the M paratuberculosis antigens p35, p36 and the 32k mycobacterial associated antigen termed HupB protein. These data suggest a causal role for mycobacteria in at least a proportion of patients with Crohn's disease. Identification of the subgroup of Crohn's disease patients infected with M paratuberculosis has been hampered due to the lack of a simple and specific serodiagnostic test to identify those who would be candidates for anti- mycobacterial therapy. The long-range objective of this proposal is to confirm M paratuberculosis p35/ p36 antigens as serologic markers and to test whether there are specific clinical/pathologic stratification(s) that correlate with their presence. We will assess the presence of M paratuberculosis infection in Crohn's disease patients by serologic testing of sera from patients and controls and in situ hybridization for the detection of the cell wall-deficient form of M paratuberculosis in involved diseased tissues. We will also use the laser capture microdissection technique to test whether M paratuberculosis are present in granulomas of Crohn's disease patients. The results from serology and molecular studies will be compared with the clinical/pathological information and demographic and epidemiologic data gathered about each patient as well as with outcome of anti-mycobacterial therapy. The results of this study should either confirm or refute the proposed etiologic association of M. paratuberculosis and Crohn's disease as well as the identification of patients with Crohn's disease and M. paratuberculosis.

描述（由申请人提供）：克罗恩病是一种特发性非- 干酪性肉芽肿病 提出的病因之一是感染 鸟分枝杆菌（Mycobacterium avium subsp.）副结核分枝杆菌（M.副结核病）， 反刍动物克罗恩病（Johne病）的病原体。 支持克罗恩病副结核分枝杆菌感染的最新证据 包括：1）从克罗恩病组织和母乳中分离， 培养，2）通过PCR测定法在组织中鉴定，3）作为 通过原位杂交，在组织中形成细胞壁缺陷，4）长的 在越来越多的克罗恩病患者中， 使用抗分枝杆菌疗法，和5）通过与M 副结核抗原p35、p36和32k分枝杆菌相关抗原 称为HupB蛋白。 这些数据表明， 在至少一部分克罗恩病患者中存在分枝杆菌。 克罗恩病患者感染M的亚组鉴定 由于缺乏简单而具体的方法， 血清诊断试验，以确定谁将是候选人的抗- 分枝杆菌治疗 这项建议的长远目标是 确认副结核分枝杆菌p35/p36抗原作为血清学标志物， 是否存在特定的临床/病理分层， 与他们的存在有关。 我们将评估M的存在 克罗恩病患者副结核杆菌感染的血清学检测 来自患者和对照的血清和原位杂交用于检测 细胞壁缺陷型副结核分枝杆菌涉及病变 组织中 我们还将使用激光捕获显微切割技术来测试 克罗恩病肉芽肿中是否存在副结核分枝杆菌 患者 血清学和分子生物学研究的结果将进行比较 根据临床/病理学信息以及人口统计学和流行病学 收集的每例患者的数据以及抗分枝杆菌治疗的结果 疗法 这项研究的结果应该证实或反驳 提出了M.副结核病和克罗恩病， 以及克罗恩病和M. 副结核病