(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.
Showing the most recent 10 out of 32 publications
