RISK FACTORS AND GASTRIC DISEASE IN PEDIATRIC H PYLORI

描述(取自应用程序) 幽门螺杆菌(Hp)是世界范围内慢性活动期的主要病因 胃炎，原发性十二指肠溃疡，与胃癌有关。多数 幽门螺杆菌感染是在儿童时期获得的；为什么有些人会患上 症状性疾病与其他疾病的关系尚不清楚。组织病理学研究 提示炎性细胞浸润的程度和类型 幽门螺杆菌感染儿童的胃十二指肠病变明显不同 与成年人相比。然而，这些差异仍然无法解释。研究 儿童初次感染幽门螺杆菌后的宿主免疫反应 与Hp毒力因子(即VacA)的关系 评估宿主感染的危险因素对于了解 幽门螺杆菌感染的发病机制。我室幽门螺杆菌感染的初步研究 儿童发展了准确的非侵入性感染检测方法 并显示出一种独特的胃粘膜炎症反应 巨噬细胞的数量。在体外，我们证明了IL-8和 Rantes趋化因子用于白细胞的激活和募集。此外，我们 显示幽门螺杆菌感染和感染的T细胞反应不同 未感染的病人。总体假设：在感染Hp的儿童中， 是宿主因素(即种族)和环境辅助因素(即水 来源)会导致症状性疾病，而有症状的儿童将 被强毒的Hp菌株感染，并有更显著的粘膜 炎症反应。具体目标：1)确定主办因素和 儿童幽门螺杆菌感染症状性感染的环境辅助因素 4个中心的Hp感染症状性内窥镜检查病例将与 年龄、性别和地区匹配的Hp感染无症状对照。2) 描述相关的细菌特性(即，表型、基因) 患有儿童幽门螺杆菌感染。幽门螺杆菌的表型和基因分型 从感染病例中获得的分离株将与 胃十二指肠疾病严重程度。3)描述宿主炎症的特征 幽门螺杆菌感染儿童的反应。组织病理学与组织病理学比较 感染儿童胃粘膜趋化因子与细胞反应 将会被确定。拟议的研究提供了一个系统的检验。 幽门螺杆菌菌株与宿主暴露特征之间的关系以及 儿童临床疾病的严重程度。这些研究是 初步了解宿主与细菌相互作用的前提条件 胃十二指肠炎症的感染和演变 幽门螺杆菌的发病机制。

DESCRIPTION (taken from the application) Helicobacter pylori (Hp) is the major cause world-wide of chronic-active gastritis, primary duodenal ulcers, and is linked to gastric cancer. Most Hp infections are acquired in childhood; why some individuals develop symptomatic disease and others do not is unclear. Histopathological studies suggest that the degree and type of inflammatory infiltrate in gastroduodenal lesions are significantly different in Hp-infected children compared to adults. However, these differences remain unexplained. Studies of the host immune response following initial Hp infection in childhood and the relationship to Hp virulence factors (i.e., vacA) bolstered by the evaluation of host risk factors for infection are critical to understand the pathogenesis of Hp infection. Our preliminary studies of Hp infection in children developed accurate non-invasive methods for detection of infection and showed a unique gastric mucosal inflammatory response with increased numbers of macrophages. In vitro, we demonstrated the impotence of IL-8 and RANTES chemokines for leukocyte activation and recruitment. Furthermore, we demonstrated a difference in the T-cell responses of Hp-infected versus uninfected patients. Overall hypothesis: among Hp infected children, there are host factors (i.e., ethnicity) and environmental cofactors (i.e., water source) which result in symptomatic disease and children with symptoms will be infected by virulent Hp strains and have a more significant mucosal inflammatory response. Specific aims: 1) determine the host factors and environmental cofactors necessary for symptomatic Hp infection in children. Hp-infected symptomatic endoscopy cases at 4 centers will be compared to age, gender and region-matched Hp-infected asymptomatic controls. 2) characterize the bacterial properties (i.e., phenotype, genotype) associated with pediatric Hp infection. The phenotype and genotype prevalence of Hp isolates obtained from infected cases will be evaluated in comparison to gastroduodenal disease severity. 3) characterize the host inflammatory response of Hp-infected children. The histopathology in comparison to the chemokine and cellular response in the gastric mucosa of infected children will be determined. The proposed research provides a systematic examination of the association between Hp strains and host exposure characteristics and the severity of clinical disease in children. These studies are prerequisite for understanding the host-bacterial interaction in initial infection and evolution of gastroduodenal inflammation and overall pathogenesis of Hp.