The overall objective of this grant is to understand the role of indoor allergens in asthma. The importance of this study comes from the extraordinary prevalence of the disease, i.e. -8 percent of the population, and the very large numbers of patients who require treatment for acute asthma, i.e. more than 1 million cases per year. Central to these studies is the view that the immune response in susceptible children [which includes IgE antibodies (ab), IgG ab, IgG4 ab and Th2 cells] is dependent on exposure. The proposed studies involve epidemiology, techniques for measuring exposure, detailed evaluation of the immune response, and studies of the acute episodes. There are two contrasting views about the nature of the immune response in non-allergic individuals: (1) that they are non-responders (immune ignorance); or (2) that they have made an alternative form of immune response. During the last two years it has become clear that the presence of a cat in the home is associated with a decreased risk of asthma and that high exposure to cat allergen can induce a different immune response that includes IgG and IgG4 antibodies, but not IgE ab. This modified Th2 response provides an opportunity to investigate: the dose response relationship between allergen exposure and the risk of asthma; the nature of the immune response to allergens in allergic and non-allergic individuals; and the aspects of the immune response that create the risk of asthma. These results suggest that the dose response relationship between exposure and sensitization is bell-shaped for cat allergen and linear for dust mite allergen. The experiments proposed will focus on: (I) the analysis of the relationship between exposure, serum antibody responses to indoor allergens, and the risk of asthma in prospective studies on three cohorts of children; (II) detailed investigation of the response of circulating T cells to mite and cat allergens using natural allergens, recombinant proteins and overlapping peptides spanning each of the molecules. These studies will evaluate differences in T cell epitope recognition, cytokine responses in vitro and cell surface phenotype of T cells from subjects with different exposure and different immune responses. (III) Investigation of the relationship between allergic responses and acute episodes of asthma using three approaches: following patients prospectively; experimental rhinovirus challenge of allergic and non-allergic individuals; as well as investigating patients presenting with asthma to the Emergency Room or hospital. The studies proposed have important implications for asthma treatment using allergen avoidance, or for novel strategies for allergen specific immunotherapy.
| Wilson, Jeffrey M; Workman, Lisa; Schuyler, Alexander J et al. (2018) Allergen sensitization in a birth cohort at midchildhood: Focus on food component IgE and IgG4 responses. J Allergy Clin Immunol 141:419-423.e5 |
| Schuyler, Alexander J; Wilson, Jeffrey M; Tripathi, Anubha et al. (2018) Specific IgG4 antibodies to cow's milk proteins in pediatric patients with eosinophilic esophagitis. J Allergy Clin Immunol 142:139-148.e12 |
| Muehling, Lyndsey M; Turner, Ronald B; Brown, Kenneth B et al. (2018) Single-Cell Tracking Reveals a Role for Pre-Existing CCR5+ Memory Th1 Cells in the Control of Rhinovirus-A39 After Experimental Challenge in Humans. J Infect Dis 217:381-392 |
| Schuyler, Alexander J; Tripathi, Anubha; Workman, Lisa J et al. (2018) Underestimation of specific IgE measurements using extract-based assays on undiluted sera revealed through dilution. J Allergy Clin Immunol Pract 6:1070-1072.e4 |
| Lawrence, Monica G; Palacios-Kibler, Thamiris V; Workman, Lisa J et al. (2018) Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID). J Clin Immunol 38:225-233 |
| Hoyt, Alice E W; Chapman, Martin D; King, Eva M et al. (2018) Food allergen component proteins are not detected in early-childhood vaccines. J Allergy Clin Immunol Pract 6:677-679 |
| Smith, Anna R; Knaysi, George; Wilson, Jeffrey M et al. (2017) The Skin as a Route of Allergen Exposure: Part I. Immune Components and Mechanisms. Curr Allergy Asthma Rep 17:6 |
| Erwin, Elizabeth A; Rhoda, Dale A; Redmond, Margaret et al. (2017) Using Serum IgE Antibodies to Predict Esophageal Eosinophilia in Children. J Pediatr Gastroenterol Nutr 65:520-525 |
| Wilson, Jeffrey M; Schuyler, Alexander J; Schroeder, Nikhila et al. (2017) Galactose-?-1,3-Galactose: Atypical Food Allergen or Model IgE Hypersensitivity? Curr Allergy Asthma Rep 17:8 |
| Knaysi, George; Smith, Anna R; Wilson, Jeffrey M et al. (2017) The Skin as a Route of Allergen Exposure: Part II. Allergens and Role of the Microbiome and Environmental Exposures. Curr Allergy Asthma Rep 17:7 |
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