The Role of Mycobacteria in Crohn's Disease

描述(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。 和鸟分枝杆菌亚种。副结核(副结核分支杆菌) 反刍动物类克罗恩病(约翰氏病)的病原体。 支持克隆氏病患者感染副结核杆菌的最新证据 包括：1)从克罗恩病组织和母乳中分离出它 培养，2)用聚合酶链式反应进行组织鉴定，3)它的检测是 通过原位杂交在组织中形成细胞壁缺陷，4)长的 越来越多的克罗恩患者的长期缓解(可能治愈) 使用抗分枝杆菌疗法，以及5)通过与M 副结核抗原p35、p36和与32k相关的分枝杆菌 称为HupB蛋白的抗原。这些数据表明， 至少有一部分克罗恩病患者体内存在分枝杆菌。 克隆氏病患者M亚群的鉴定 由于缺乏一种简单和特异的方法，副结核病一直受到阻碍 血清诊断试验，以确定哪些人可能是抗- 分枝杆菌疗法。这项建议的长期目标是 确定副结核分枝杆菌p35/p36抗原为血清学标志并进行检测 是否有特定的临床/病理分层(S) 与它们的存在相关联。我们将评估M的存在 克隆氏病患者副结核感染的血清学检测 用原位杂交法检测患者和对照组血清中的甲胎蛋白 受累副结核分枝杆菌的细胞壁缺陷型 纸巾。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支杆菌 病人。血清学和分子研究的结果将进行比较。 临床/病理信息以及人口学和流行病学 收集的每个患者的数据以及抗分枝杆菌的结果 心理治疗。这项研究的结果应该要么证实，要么驳斥 副结核分枝杆菌与克罗恩病的病因学联系 以及克罗恩病患者和M。 副结核。

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.