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Title: Risk factors for peanut sensitization and allergy : novel disease and gene-environment interactions and biomarkers of disease
Author: Brough, Helen Annaruth
ISNI:       0000 0004 5368 5007
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2015
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Background: Peanut allergy (PA) is responsible for life-threatening allergic reactions. Household peanut consumption (HPC), used as an indirect measure of environmental peanut exposure (EPE), is associated with PA especially when compared against atopic controls. Aims: To determine the association between EPE, peanut sensitization (PS), PA and explore the modifying effect of an impaired skin barrier. To assess the route of PS using peanut specific immune responses in skin versus gut derived T-helper (Th) cells. Methods: Peanut antigen in dust was assessed using ELISA, Mass Spectrometry (MS) and basophil activation test (BAT). HPC was compared to peanut-dust levels and airborne peanut. The impact of EPE on PS was determined in three cohorts with genotypic and phenotypic skin barrier function measures. Recall responses to peanut in skin versus gut-homing memory Th-cells were assessed using gene expression profiles and intracellular cytokine staining. Results: HPC was the most important factor for peanut-dust in the infants’ environment. BAT confirmed biological activity of peanut in dust; MS confirmed whole sequences of major peanut allergens. Airborne peanut was only transiently above peanuts being shelled. Early EPE increased the risk of PS; this was augmented by atopy and markers of skin barrier impairment. Th2 gene expression was not increased in skin versus gut-homing memory CD4+Th cells from peanut allergic children. IL9 was the most accurate classifier for PA versus PS and atopic non-peanut allergic (NA) children. Conclusions: EPE is a risk factor for PS in atopic children, especially when skin barrier is impaired; this supports the concept of epicutaneous peanut sensitization. Peanut is unlikely to be sufficiently airborne to induce inhalational sensitization. Although, there was no differential expression of Th2 cytokines in skin versus gut-homing Th cells, longitudinal assessment as children progress from PS to PA may show Th2 cytokines initiate in skin-homing Th cells then spread to gut-homing Th cells. IL9 may be a useful biomarker for peanut allergy. The role of IL9 in mast cell activation, trafficking and proliferation also provides a compelling explanation for the immunobiology underlying epicutaneous sensitization and elicitation of allergic reactions.
Supervisor: Turcanu, Victor ; Perkin, Michael Richard ; Lack, Gideon Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available