Atopic dermatitis (AD) or atopic eczema is the third condition making up the atopic triad (asthma, hayfever and eczema). It usually has its onset before two years of age. It is common, affecting approximately 10% of Australian children and 7% of Australian adults, and is increasing in prevalence. As with asthma, genes are known to be important in its causation, and several different genes have been reported to be involved by different investigators. These findings are not always repeatable in di ....Atopic dermatitis (AD) or atopic eczema is the third condition making up the atopic triad (asthma, hayfever and eczema). It usually has its onset before two years of age. It is common, affecting approximately 10% of Australian children and 7% of Australian adults, and is increasing in prevalence. As with asthma, genes are known to be important in its causation, and several different genes have been reported to be involved by different investigators. These findings are not always repeatable in different countries or ethnic groups. One, the mast cell chymase gene seems to be associated with AD in Japan, but not in Australia or Italy. However, this gene may be responsible only for AD where total serum Immunoglobulin E is low, roughly 20% of all AD. Therefore, the previous studies may not have included enough cases of this subtype to reliably detect the association. The present study aims to test all the published genes in two panels of families: one where both AD and asthma or hayfever are present in the family (180 families), the second where AD alone is present (100 families). We will also test for genetic linkage to particular regions of the genome, where the specific gene is yet to be identified, and for newly discovered gene variants in these regions that may be associated with AD. Confirming and refining the nature of genes involved in the causation of AD is useful for the basic understanding of biochemical pathways to disease and ultimately to the design of drugs to interfere with these pathways.Read moreRead less
Effects Of Enteric Microflora On Mucosal And Systemic Immune Development In Infants At Risk Of Allergic Disease
Funder
National Health and Medical Research Council
Funding Amount
$219,750.00
Summary
The increase in allergic diseases over the last 20-30 years has been attributed to an increased immunological propensity to Type-2 allergic immune responses in the postnatal period. It has been proposed that this may be due to a relative deficiency of counter-regulatory Type 1 immune responses in early life. Thus, there is growing interest in factors that might affect Type 1 maturation in this early period. It has been proposed that progressively cleaner societies may have more allergies because ....The increase in allergic diseases over the last 20-30 years has been attributed to an increased immunological propensity to Type-2 allergic immune responses in the postnatal period. It has been proposed that this may be due to a relative deficiency of counter-regulatory Type 1 immune responses in early life. Thus, there is growing interest in factors that might affect Type 1 maturation in this early period. It has been proposed that progressively cleaner societies may have more allergies because there is less stimulation of the Type 1 responses during immune development. Bacterial products provide important maturation signals to the developing immune system, and may favour Type 1 responses. The largest early exposure to bacteria in occurs in the human gut, which is colonised with bacteria soon after birth. These bacteria play an important role in maintaining health, both in the protection from harmful bacteria, and in the development of food tolerance. There is evidence that infants in cleaner sociaeties may have alterations in bowel flora. For many years probiotic formulations (containing strains of these healthy bacteria) have been used safely to treat children with gastroenteritis to reduce the duration of diarrhoea. More recently it has been suggested that these formulations have a role in treating and even preventing allergic disease. Further research is needed to confirm this, and to define the underlying immunological processes. This randomised double blind control study will determine if supplementation with probiotic flora (in late pregnancy and in early infancy) can favourably influence gut colonisation, alter subsequent immune development, and help prevent allergic disease in infants at high risk (from allergic families).Read moreRead less
This project will examine new ways in which the major effector cells of allergy migrate to sites of inflammation, such as the lung and the skin and are activated locally by a novel S100 protein mediator. We have found a natural protein of the innate immune system, present in macrophages and neutrophils in the lungs of patients with acute fatal asthma, which activates mast cells causing release of mediators that trigger asthma attack. We have identified a potential receptor for this protein on hu ....This project will examine new ways in which the major effector cells of allergy migrate to sites of inflammation, such as the lung and the skin and are activated locally by a novel S100 protein mediator. We have found a natural protein of the innate immune system, present in macrophages and neutrophils in the lungs of patients with acute fatal asthma, which activates mast cells causing release of mediators that trigger asthma attack. We have identified a potential receptor for this protein on human mast cells grown in culture. We will characterise the chemical nature of this receptor and verify that it is functionally important in mast cell activation. Because mast cells reside in almost all body tissues and are also important mediators of host responses to infection and in chronic inflammation such as rheumatoid arthritis and psoriasis, our studies may indicate novel and unexpected ways in which they are activated. Another key cell in allergic and parasitic diseases is the eosinophil. We have found that two other S100 proteins are expressed in eosinophils from the blood of normal individuals and that the genes that encode these proteins are regulated by mediators that regulate eosinophil migration and survival at allergic sites. However although the numbers these cells are high in lung biopsies from patients with asthma, we find that these proteins are generally not expressed. Because one of the S100 proteins, S100A9, was recently found to be important in the ability of other blood cells to migrate to signals that recruit them into tissues, we will examine whether this protein regulates the ability of eosinophils to migrate. Results from this project will provide new knowledge concerning mechanisms of allergy and may lead to the design of novel strategies to regulate the process. Results may have broader ramifications applicable to other inflammatory and infectious diseases.Read moreRead less