PROJECT SUMMARY/ABSTRACTEosinophilic esophagitis (EoE) is an atypical form of food allergy, in that the patients do not experienceimmediate symptoms in the mouth, in the skin or in the esophagus following exposure to relevant foods.Nonetheless many or most of the children with EoE get better, both symptomatically and histologically, over 2-3 months on a diet excluding specific foods including cows' milk (CM) and/or wheat. It is known that manychildren with EoE have detectable, but low-titer IgE antibodies (Ab) to CM, wheat or egg proteins. It has alsobeen reported that adults with EoE have IgG4 Ab specific for relevant foods. Recently we have demonstratedthat children with EoE have high or very high titers of IgG4 Ab to proteins from CM or wheat. These responsescan be as high as 100 Âµg/ml of IgG4 Ab, which is as high as any specific IgG4 responses previously reported.In comparison with an age-matched unselected cohort there was a very strong association (odds ratios as highas 15) between sIgG4 to CM proteins ? 10 Âµg/ml and a diagnosis of EoE. This association was particularlystrong among boys aged 10-18, although there were too few girls and young children in the cohort to draw firmconclusions about the effects of age or sex on the IgG4 response to CM proteins. Thus, the main objectivehere is to expand the size of the cohort to be able to gain more evidence about the effects of age, sex and/orCM consumption on specific IgG4 levels. This will include a larger number of young children with EoE, but alsomales and females extending into early adulthood. As part of the case-control design the study will involverecruitment of age-similar young children and young adults that are unselected for allergic disease. The resultsfrom these studies will form a foundation for future prospective investigations into whether measurement ofserum IgG4 and/or IgE to specific foods could have utility as a non-invasive tool for diagnosis and/ormanagement of EoE. An additional objective will be to investigate the significance of our recent finding thatover 10% of adolescent children from an unselected birth cohort had high-titer IgG4 Ab to CM proteins. Despitebeing less prevalent than in EoE children, this finding suggests that the immune response that contributes toEoE is relatively common in the general population and raises the possibility that esophageal eosinophilia (orlatent EoE) may be more prevalent in the community than currently appreciated. To address this, control adultswho are identified as having high-titer sIgG4 Ab specific for CM and/or wheat proteins will be invited foresophagoscopy and biopsy.