Although there has been a great deal of investigation into the pathogenesis of the allergic immune response, there is very little understanding of how natural allergen exposure influences the ensuing allergen-specific immune responses, and whether atopic disposition modifies allergen exposure-immune response relationships. In the proposed study, an occupational model of allergen exposure will be used to test the overarching hypothesis that the level of natural exposure to mouse allergen influences the subsequent immune responses to the major mouse allergen, Mus m 1, and ultimately, the clinical allergy phenotype. To test these hypotheses, we will continue to follow workers at The Jackson Laboratory (TJL) who are currently enrolled in a prospective cohort study, the JAXCohort Study, and recruit additional new workers into the cohort.
The specific aims are as follows: (1) To continue to repeatedly assess mouse allergen exposure, mouse allergen-specific humoral responses, and clinical allergy phenotype in currently and newly enrolled participants;(2) To assess the diversity of IgG, IgG4, and IgE mouse allergen epitope repertoires among current and newly enrolled participants;(3) To assess mouse-specific Tr1 cell frequency in newly enrolled participants;and (4) To assess IgE-mediated function by assessing basophil phenotypes and Mus m 1 uptake by antigen presenting cells in newly IgE-sensitized cohort members. We will examine relationships between allergen exposure levels and these allergen-specific immune responses and clinical allergy phenotype. The proposed prospective cohort study, in a setting in which repeated assessments of personal allergen exposure are feasible, is arguably the best approach to understanding these complex, time- and exposure-dependent relationships. Findings from this study will result in a better understanding of the natural history of allergen exposure and immune responses that will provide a foundation for the development of immunomodulatory strategies aimed at prevention and treatment of allergic diseases.
A more detailed understanding of the relationship between allergen exposure and disease is needed to develop better preventive and treatment strategies. We will take advantage of the ability to study dose-response relationships more precisely in an occupational setting as a model to address this relationship. We will compare aspects of our findings in these workers to people with mouse allergy living with high levels of allergen in inner city Baltimore in the hope that the knowledge gained from this study will provide the foundation upon which to devise preventive and therapeutic interventions in occupational and community settings.
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