Dr Belinda J Hales and Professor Wayne R Thomas
Project title: IgE facilitated CD23 binding assay
Project description: House dust mite (HDM) allergic children attending the emergency department for exacerbations of asthma show the same profile of allergic sensitisation to children without disease as judged by IgE anti-allergen antibodies. They do however show a marked reduction in IgG antibodies indicating IgG antibodies could be protective in preventing allergic disease. The protective affect of IgG antibodies is supported by pollen immunotherapy trials where the improvement of symptoms was associated with the ability of IgG antibodies to block the IgE-allergen complexes to the low affinity CD23 IgE receptor.
Few laboratories have measured IgE facilitated CD23 binding and blocking of CD23 binding by IgG as the current cell-dependent assay is technically cumbersome. This study will develop a more quantitative CD23 binding assay that uses standard reagents and has high throughput capabilities. The CD23 binding assay will then be used to test differences in IgE-mediated facilitated allergen binding (FAB) and blocking of binding by IgG in HDM-sensitised asthmatic and healthy children with similar IgE titres. It is expected that the binding and blocking of binding will vary with the severity of disease. This will be the first study of IgG blocking of IgE mediated FAB in allergic sensitisation (without immunotherapy) and the first study in HDM allergy and asthma.
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Dr Anthony Kicic, Professor Stephen Stick and Associate Professor Paul Rigby
Project title: Identification of intrinsically abnormal processes in asthmatic epithelium independent of atopy.
Project description: Although evidence is emerging that abnormal epithelium is commonly observed in asthma, few studies have addressed whether these abnormalities are intrinsic to asthma. For example, it is commonly the case, even in seminal studies, to compare results obtained using samples from atopic asthmatics with results obtained from nonatopic or unclassified (with regard to atopy) controls. Furthermore, rarely have samples been obtained from subjects with mild disease or from children and therefore it is impossible to determine to what extent observations are due to primary abnormalities, secondary to chronic inflammation or in fact due to atopy rather than asthma. This conceptually simple project aims to address a fundamental gap in our understanding of asthma. We have identified an important deficiency in the published literature that has arisen because of a focus on “atopic asthma”. As a consequence intrinsic abnormalities of the epithelium common to both atopic & non-atopic asthma are likely to have been overlooked. We will use a unique resource of airway epithelial cells (AEC) obtained from an unselected population of children. The nature of the population is such that we will study steroid naive children with infrequent, mild asthma. Therefore, compared with many published studies our observations are unlikely to be complicated by the effects of chronic inflammation. The proposed study will determine whether there is an intrinsic abnormality of barrier function in asthma that is also independent of atopy. We believe that the outcomes of this research have the capacity to significantly influence the research agenda with regard to the mechanisms of childhood asthma.
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2010 New Investigator Grant
Dr Svetlana Baltic and Dr Phillip Thompson
Project title: What is the role of PGE2 and EP receptors in epithelial cell function in asthma?
Project description: PGE2 has a prominent role in inhibiting airway inflammation in asthma. Airway epithelial cells promote, maintain and regulate airway inflammation by producing pro-inflammatory, eosinophil and neutrophil-associated cytokines and chemokines. Despite airway epithelial cells expressing all four known PGE2 receptors, little is known about how PGE2 influences human lung epithelial function. We hypothesise that the nature of the anti-inflammatory effects depends upon which PGE2 receptor is activated. This research seeks to characterise the role of each PGE2 receptor in terms of epithelial cell function. This knowledge will open up the possibility of new specific treatments for inflammatory airway diseases.
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