RISK FACTORS AND GASTRIC DISEASE IN PEDIATRIC H PYLORI

儿科幽门螺杆菌的危险因素和胃病

• 批准号: 2796618
• 负责人: BENJAMIN David GOLD
• 金额: $ 21.76万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2002-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2796618
• 关键词: Helicobacter; T lymphocyte; child (0-11); clinical research; cytokine; disease /disorder proneness /risk; gastrointestinal disorder; gastrointestinal infection; histopathology; human subject; leukocyte activation /transformation; mucosal immunity; polymerase chain reaction; virulence; western blottings

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.

描述（取自应用程序） 幽门螺杆菌（Helicobacter pylori，Hp）是世界范围内慢性活动性胃炎的主要病因 胃炎，原发性十二指肠溃疡，并与胃癌有关。最 Hp感染是在儿童时期获得的;为什么有些人会发展 有症状的疾病和其他不清楚。组织病理学研究 表明，炎症浸润的程度和类型， 幽门螺杆菌感染儿童胃十二指肠病变有显著差异 与成年人相比。然而，这些差异仍然无法解释。研究 儿童期初始Hp感染后的宿主免疫反应， 与Hp毒力因子的关系（即，vacA）， 评估宿主感染的风险因素对于了解 Hp感染的发病机制。我们对幽门螺杆菌感染的初步研究 儿童发展出准确的非侵入性方法来检测感染 并显示出独特的胃粘膜炎症反应， 巨噬细胞的数量在体外实验中，我们证明了IL-8和 用于白细胞活化和募集的RANTES趋化因子。而且我们 证实了Hp感染者与 未感染的患者总体假设：在Hp感染儿童中， 是宿主因素（即，种族）和环境辅因子（即，水 源），导致症状性疾病，有症状的儿童将 被强毒Hp菌株感染，并具有更显著的粘膜 炎症反应。具体目标：1）确定宿主因素， 儿童症状性Hp感染所必需的环境辅助因子 将比较4个中心的Hp感染症状性内镜检查病例， 年龄、性别和地区匹配的Hp感染无症状对照。（二） 表征细菌特性（即，表型，基因型）相关 儿童幽门螺杆菌感染幽门螺杆菌的表型和基因型 将对从感染病例中获得的分离株进行评价， 胃十二指肠疾病严重程度。3)表征宿主炎症 Hp感染儿童的反应。组织病理学与 感染儿童胃粘膜中趋化因子和细胞反应 将被确定。拟议的研究提供了一个系统的检查 Hp菌株与宿主暴露特征之间的关联， 儿童临床疾病的严重程度。这些研究 了解宿主-细菌相互作用的先决条件 感染和胃十二指肠炎症演变以及总体 幽门螺杆菌的致病机制