Risk factors for gastric disease in pediatric H. pylori

儿童幽门螺杆菌胃病的危险因素

• 批准号: 7067023
• 负责人: BENJAMIN David GOLD
• 金额: $ 4.34万
• 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 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7067023
• 关键词: Risk; factors; gastric; disease; pediatric

EXCEED THE SPACE PROVIDED. Helicobacter pylori (Hp) is a major cause of chronic-active gastritis, primary duodenal ulcers and strongly linked to gastric cancer. Most Hp infections worldwide are acquired in childhood. Why some individuals develop symptomatic disease is unclear and, until recently, no studies critically evaluated the role of pediatric Hp strains and/or host factors in disease outcomes. Over the past 5 years of NIH funding, 486 children from Atlanta, Cleveland, and Miami were enrolled; 184 (38%) were Hp-infected. Race (African American) and younger age, in conjunction with Hp strains expressing cagA and vacAslB, were shown to be risk factors for both esophageal and gastric disease; suggesting a different disease paradigm from Hp-infected adults. Using the Updated Sydney system, we demonstrated a histopathologic spectrum in children, which included novel observations of atrophic gastritis with intestinal metaplasia. Overall hypothesis for competitive renewal: disease manifestations in Hp-infected children are influenced by specific host factors (i.e., race), environmental exposures, and specific virulence factors of infecting Hp strains. Specific aims: 1) further characterize specific host factors and environmental exposures contributing to symptomatic childhood infection emphasizing follow up of 2 established specific cohorts to ascertain immune response natural history, and targeted enrollment in specific age, gender and demographic strata to facilitate detection of significant differences not attained previously. 2) Utilize gene-array technology for whole Hp genome assessment and proteomic analysis of specific virulence determinants associated with pediatric Hp strains. 3) Further characterize the host immunologic and mucosal response in Hp-infected children. Hp-infected symptomatic endoscopy cases at our established 3 clinical centers of high, moderate and low Hp prevalence will be compared with age-matched Hp-infected asymptomatic and uninfected symptomatic controls. The Updated Sydney system will be employed to assess gastric histopathology severity and phenotype in follow-up of the two "novel" cohorts established in the past 5 years; a) atrophic gastritis; b) esophageal and gastric disease group enabling a comprehensive, multivariate evaluation of the natural history of Hp-infected children in two distinct disease paradigms, and, new cases in specific age, gender and demographic strata. Using molecular methods (multiplex [MP]-PCR, RT-PCR) and a micro ELISPOT assay on peripheral blood mononuclear cells (PBMCS), Thl, Th2, Th3 or balanced Thl/Th2 response will be determined to further characterize the Hp-infected child's immune response phenotype. We propose to further our previous work with critically lacking studies from a multivariate approach leading to a better understanding of the gastroduodenal disease sequelae and overall pathobiology of Hp infection in humans. PERFORMANCE SITE ========================================Section End===========================================

超出所提供的空间。 幽门螺杆菌（Helicobacter pylori，Hp）是慢性活动性胃炎、原发性十二指肠溃疡的主要病因，与胃癌密切相关。全世界大多数Hp感染是在儿童时期获得的。为什么有些人发展为症状性疾病尚不清楚，直到最近，没有研究严格评估小儿Hp菌株和/或宿主因素在疾病结局中的作用。在过去5年的NIH资助中，来自亚特兰大、克利夫兰和迈阿密的486名儿童入组; 184名（38%）为Hp感染者。种族（非裔美国人）和年轻的年龄，结合Hp菌株表达cagA和vacAslB，被证明是食管和胃疾病的危险因素，这表明一个不同的疾病模式从Hp感染的成年人。使用更新的悉尼系统，我们证明了一个组织病理学谱的儿童，其中包括新的观察萎缩性胃炎伴肠上皮化生。竞争性更新的总体假设：Hp感染儿童的疾病表现受特定宿主因素的影响（即，种族），环境暴露和感染Hp菌株的特定毒力因子。具体目标：1）进一步表征导致症状性儿童感染的特定宿主因素和环境暴露，强调对2个已建立的特定队列进行随访，以确定免疫应答自然史，并在特定年龄、性别和人口统计学分层中进行有针对性的招募，以促进检测先前未达到的显著差异。2)利用基因阵列技术进行全Hp基因组评估和与儿童Hp菌株相关的特定毒力决定因素的蛋白质组学分析。3)进一步描述Hp感染儿童的宿主免疫和粘膜反应。在我们建立的高、中和低Hp流行率的3个临床中心，将Hp感染的有症状的内镜检查病例与年龄匹配的Hp感染的无症状和未感染的有症状对照进行比较。将采用更新的Sydney系统评估过去5年中建立的两个“新”队列随访中的胃组织病理学严重程度和表型; a）萎缩性胃炎; B）食管和胃疾病组，从而能够对两种不同疾病模式中的Hp感染儿童的自然史以及特定年龄、性别和人口统计学分层中的新病例进行全面、多变量评价。使用分子方法（多重[MP]-PCR、RT-PCR）和外周血单个核细胞（PBMCS）的微量ELISPOT测定，将确定Th 1、Th 2、Th 3或平衡的Th 1/Th 2应答，以进一步表征Hp感染儿童的免疫应答表型。我们建议进一步我们以前的工作，严重缺乏的研究，从多变量的方法，导致更好地了解胃十二指肠疾病的后遗症和整体的人类幽门螺杆菌感染的病理生物学。性能现场=