The Updated Sydney system will be applied to assess severity of gastric histopathology, and immunohistochemistry performed on formalin-fixed, paraffin embedded tissues to phenotype mucosal disease (i.e., character, severity) in newly enrolled cases in specific age, gender and demographic strata and the two "novel" cohorts established in our previous studies; i) atrophic gastritis cohort; ii) esophageal and gastric disease cohort, affording insight into the natural history of the immune response in Hp-infected children in two different disease paradigms. Both molecular methods and a novel micro ELISPOT performed on PBMCS and gastric T-cells to determine Th1, Th2 or balanced Th1/Th2 response will be used to further characterize the Hp-infected child's immune phenotype. During the latter 2 years of the proposed studies, PBMC chemokine response will then be compared to the mucosal/cellular response using RT-PCR and gene array. The data obtained from aims 1 and 3 will be integrated with that obtained in aim 2 (Hp-strain genotype) in order to develop a model to predict disease outcome based on host demographics, strain type and inflammatory/immune response. These studies are critical to understand and better predict the gastroduodenal disease sequelae and overall pathobiology of Hp infection in humans.