Monash University
20170306-Ashley-Thesis.pdf (6.59 MB)

Genomic Pathways Underlying IgE-Mediated Paediatric Food Allergy

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posted on 2017-03-14, 23:35 authored by Sarah Elizabeth Ashley
The prevalence of food allergy has risen drastically over the past 15-20 years. Due to this rapid time frame underlying mechanisms of the condition are still poorly understood. In contrast, the genetic architecture of other allergic conditions such as eczema and asthma have been studied over a larger time frame and are known to be complex diseases with numerous genetic and environmental risk factors contributing to the development of the condition. Early life environmental exposures are thought to be major determinants in the  onset of food allergy and many such factors have been identified and thoroughly examined in epidemiological studies. However, genetic polymorphisms are also known to mediate food allergy risk and it is likely that heritable factors underscore individual responsiveness to environmental exposures. For example, vitamin D deficiency is linked to food allergy risk but susceptibility to this exposure is modified by polymorphisms within the vitamin D binding protein gene. Yet, while lifestyle and environmental exposures in food allergy have been well characterised and studied, genetic determinants of food allergy remain relatively under-explored.
   The theme of this thesis is the identification of genetic risk factors for IgE-mediated food allergy, expanding on a field of relative paucity in the literature. The work was undertaken on samples from a well characterised, challenge-proven food allergy cohort, HealthNuts. The first phase of the project was to examine candidate genes with strong evidence of biological plausibility from allergy literature.

   The first gene of interest was Serine peptidase inhibitor kazal type 5 (SPINK5 ) which encodes the epithelial cell shedding regulatory protein Lympho-epithelial kazal-typerelated inhibitor (LEKTI). Recently there has been increasing interest in the role of the disrupted skin barrier in the development of food allergy due to the correlation between early onset eczema and food allergy. As well as the association between loss-of-function mutations of the skin barrier gene filaggrin and development of sensitisation to foods. The second gene of interest was interleukin 13 (IL13) which encodes the immune cytokine of the same name. The IL-13 cytokine is a Th2 mediator, directly involved in the proallergic immune responses which leads to the formation of immunological memory to food allergens and the clinical manifestation of symptoms characteristic of IgE-mediated food allergy.
   Finally a genome-wide association study (GWAS) was conducted, a hypothesis-free approach to identify novel peanut allergy susceptibility loci.  Overall, a comprehensive   approach was undertaken to identify key risk genes for food allergy. Future directions for this work will be to further confirm the observed associations in international cohorts, and with larger, pooled GWAS data on IgE-mediated food allergy. These approaches will add to the current understanding of the mechanisms of food allergy and may have utility in predicting severity and/or onset of the condition.


Principal supervisor

Richard Saffery

Additional supervisor 1

David Martino

Additional supervisor 2

Katrina Allen

Additional supervisor 3

Justine Ellis

Year of Award


Department, School or Centre

Central Clinical School

Additional Institution or Organisation

Molecular and Translational Science (Hudson Institute)

Campus location



Doctor of Philosophy

Degree Type



Faculty of Medicine Nursing and Health Sciences

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    Faculty of Medicine, Nursing and Health Sciences Theses


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