Exploring The Nature, Pathophysiology, And Genetics Of Birch Pollen Induced Allergic Rhinitis And Its Overlap With Peanut Allergy Using Experimental Models And Genetic Analysis

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Authors

Tenn, Mark

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thesis

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eng

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Allergy , Allergic Rhinitis , Atopic March , Birch Pollen , Environmental Exposure Unit , Filaggrin , Group 2 Innate Lymphoid Cells , Loss-of-Function Mutation , Nasal Allergen Challenge , Nasal Lavage , Patch Testing , Peanut Allergy , Skin Sensitization

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Abstract

Birch pollen represents a significant trigger of allergic symptoms in sensitized individuals with allergic rhinitis (AR). Inhalation of birch pollen can elicit nasal and ocular symptoms, and in some patients, confer oral symptoms following ingestion of peanut-containing foods due to the cross-reactivity between birch pollen and peanut protein. These symptoms can negatively impact quality of life during in-season and out-of-season months. This thesis investigates the pathophysiology and genetics of birch pollen-induced AR using two experimental models of AR, the Environmental Exposure Unit (EEU) and the nasal allergen challenge (NAC), and genotyping analysis for mutations in the gene encoding filaggrin (FLG), a critical skin barrier protein. The EEU and NAC use contrasting methods of allergen delivery to mimic symptom manifestations associated with allergen exposure (EEU, continuous exposure with birch pollen grains; NAC, single dose nasal spray with birch pollen extract). Following birch allergen exposure, birch-allergic participants experienced a gradual increase in nasal and ocular symptoms over time in the EEU, which contrast the immediate sharp increase observed during the NAC. Responses to allergen challenge via these two models provided useful information to guide future studies of novel therapeutics. Using flow cytometric analysis, the frequency of group 2 innate lymphoid cells decreased in the blood and increased in the nose 4 hours after a NAC with birch pollen extract. The frequency of the four most prevalent FLG mutations in Caucasians in this investigation were significantly lower in birch-allergic participants compared to non-allergic controls, which contrasted current literature. When placed directly onto intact skin, birch pollen protein did not elicit allergic skin responses in these participants. Collectively, these data illustrate the distinct responses of the nasal mucosa compared to the epidermis when both were exposed to birch pollen. Additional studies with a larger sample size would be needed to address the lower rate of FLG mutations observed in individuals with birch pollen-induced AR.

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Attribution 3.0 United States
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