Immunological And Molecular Basis Of Anaphylaxis Caused By Peanut And Tree Nut Allergy
Funder
National Health and Medical Research Council
Funding Amount
$195,691.00
Summary
An allergy to nuts is estimated to affect 1% of the population and peanuts are the major cause of fatal food-induced anaphylaxis. Five deaths occurred in the UK in 1993 which attracted media attention to the gravity of this problem. Proteins in the nut trigger a massive immunological reaction that causes the body to go into anaphylactic shock in which all the major body systems shut down. Nut allergy usually presents in infancy and persists indefinitely. As nuts are used in a wider and less visi ....An allergy to nuts is estimated to affect 1% of the population and peanuts are the major cause of fatal food-induced anaphylaxis. Five deaths occurred in the UK in 1993 which attracted media attention to the gravity of this problem. Proteins in the nut trigger a massive immunological reaction that causes the body to go into anaphylactic shock in which all the major body systems shut down. Nut allergy usually presents in infancy and persists indefinitely. As nuts are used in a wider and less visible range of food products, sensitisation is increasing and occurring earlier. It has been proposed, wrongly, that peanut (groundnut) allergic patients do not suffer from allergy to tree nuts (hazel, almond, Brazil, walnut). However a British survey of 1250 patients suffering from peanut anaphylaxis revealed that 50% of people with peanut allergy are also allergic to other nuts confirming our own clinical observations. At present, unlike insect venom allergy, grass pollen allergy and house dust mite allergy, there is no preventative treatment available. We plan to explore peanut allergy and investigate cross-reactivity between peanuts and major tree nuts to attempt to identify an allergen(s) that could explain the molecular nature of the allergy and offer approaches to immunotherapy. This information is necessary if we are to achieve safe and effective allergy shots for patients with this life long and life-threatening allergy as well as assisting in the development of better diagnosticRead moreRead less
House Dust Mites, Endosymbiotic Bacteria And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$208,372.00
Summary
Asthma is a very common, chronic disease in both children and adults, with a prevalence of at least 5% worldwide. It continues to have a highly significant clinical and socio-economic impact on Western communities, despite the introduction of a variety of pharmacological treatments and there is evidence to indicate that the mortality rate from the disease is increasing. Several sources are known to be associated with asthma but the most frequently associated allergen is the house dust mite (HDM) ....Asthma is a very common, chronic disease in both children and adults, with a prevalence of at least 5% worldwide. It continues to have a highly significant clinical and socio-economic impact on Western communities, despite the introduction of a variety of pharmacological treatments and there is evidence to indicate that the mortality rate from the disease is increasing. Several sources are known to be associated with asthma but the most frequently associated allergen is the house dust mite (HDM) and allergy to it has been shown to be an independent risk factor. Our laboratory has been involved in these studies and have isolated several enzymes associated with digestion. We have also shown that the mite proteases are potent inducers of cytokines from respiratory epithelium, indicating that the biochemistry of allergens may be important in the sensitisation. During these studies, we have shown that mites produce enzymes which lysed Gram-positive bacteria. Analysis of one of these enzymes has revealed that mites are colonised by bacteria in their gut. These bacteria may well be a source of some of the allergens which provoke symptoms in asthmatic patients. In this grant proposal, experiments will be performed to assess this possibility. Such findings may have significant impact on our understanding of mite allergy as well as highlighting potentially new insights into mite control.Read moreRead less
The main purpose of this study is to understand how airborne fungi affect asthmatics who are allergic to them. Fungi or moulds release large numbers of spores into the air that are inhaled. In many cases fungal spores outnumber other particles that carry allergen, such as pollens or cat dander, by 100 to 1. This makes fungi the most common potential allergen in the environment. Fungi have been associated with respiratory diseases including fungal sinusitis, asthma, rhinitis, allergic alveolitis ....The main purpose of this study is to understand how airborne fungi affect asthmatics who are allergic to them. Fungi or moulds release large numbers of spores into the air that are inhaled. In many cases fungal spores outnumber other particles that carry allergen, such as pollens or cat dander, by 100 to 1. This makes fungi the most common potential allergen in the environment. Fungi have been associated with respiratory diseases including fungal sinusitis, asthma, rhinitis, allergic alveolitis and sick building syndrome. Largely due to their diversity and complexity, allergenic fungi have not been well studied and the ways in which individuals vary when inhaling spores is not known. Unlike other allergenic particles, it is unlikely that fungal spores release their allergen as soon as they are inhaled because we have shown in earlier in vitro studies that fungi continue to release allergen over time and this is likely to be the case when they are inhaled. Our laboratory has developed two new techniques that allow us to measure how many spores people inhale and whether they are allergic to them. This study will use these tools to detect and identify the important allergenic fungi involved in domestic and outdoor exposure of asthmatics, the degree of contribution to the total allergen load to which subjects are exposed and identify in what conditions fungi are the causal agents in location-specific symptoms. This study will also investigate allergen production of fungi in situ in the human nose, which will have application in allergic sinusitis and asthma amongst other respiratory diseases. We will investigate how readily allergenic spores germinate in the nose and under what conditions they release allergen.Read moreRead less
Initiating Events In The Development Of Allergic Airway Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$452,545.00
Summary
Despite recent advances we still do not understand the basic mechanisms which underlie the development of allergic airway inflammatory diseases such as rhinitis and asthma. It has been previously shown that when pollen are exposed to water they release a large number of very small starch granules which contain a number of potent allergens as well as plant steroids. In addition house dust mite allergens which are strongly associated with asthma are mostly located in small faecal pellets. Both the ....Despite recent advances we still do not understand the basic mechanisms which underlie the development of allergic airway inflammatory diseases such as rhinitis and asthma. It has been previously shown that when pollen are exposed to water they release a large number of very small starch granules which contain a number of potent allergens as well as plant steroids. In addition house dust mite allergens which are strongly associated with asthma are mostly located in small faecal pellets. Both these particles are ideally sized to enter the respiratory tract and initiate inflammatory responses. We have shown that these responses appear to be of the type that is needed to initiate allergic reactions. We intend to further study the interactions of these small inhaled allergen containing particles with cells of the respiratory tract. In this proposal we will look at both alveolar macrophages and respiratory epithelial cells. These approaches will not only provide new information about the processes of airway inflammation caused by allergens but may also define new therapeutic approaches to the treatment of these diseases.Read moreRead less
I am a research scientist measuring inhaled and exhaled bioaerosols, such as viruses and allergens, to determine their clinical role in human respiratory diseases, particularly asthma.
Structure-function Relationships Of Rye Grass Pollen Allergens And Preparation Of Hypoallergenic Mutants For Therapy
Funder
National Health and Medical Research Council
Funding Amount
$223,928.00
Summary
Grass pollen is an important cause of allergy (eg. hayfever, allergic asthma) world-wide affecting up to 30% of the population. In Australia, rye grass pollen is a clinically significant health problem costing $83-160 million per annum. At present, the main treatment of seasonal allergy is by pharmacotherapy with the use of crude extracts in specific immunotherapy which often causes large and annoying local skin reactions and may even cause anaphylaxis. Moreover, the use of crude extracts in dia ....Grass pollen is an important cause of allergy (eg. hayfever, allergic asthma) world-wide affecting up to 30% of the population. In Australia, rye grass pollen is a clinically significant health problem costing $83-160 million per annum. At present, the main treatment of seasonal allergy is by pharmacotherapy with the use of crude extracts in specific immunotherapy which often causes large and annoying local skin reactions and may even cause anaphylaxis. Moreover, the use of crude extracts in diagnosis of allergy among some atopic individuals may be inaccurate or ineffective. In the last eight years of my research, I have contributed significantly to the identification, characterisation and molecular cloning of grass pollen allergens. In this proposal, I aim to evaluate recombinant rye grass pollen allergens as standardised and more effective diagnostic reagents and, through the identification and better understanding of the allergenic segments of these proteins, to prepare recombinant mutants of the same proteins which are no londer allergenic. Avaliability of such non-allergenic protein reagents will provide safer immunotherapy in the future. Moreover, since the biolgical role, function and structure of such allergens in the grass pollen still remain largely unknown, I will aim to investigate this with the clinically significant allergens of rye grass pollen. Determination of biological function and structure of such allergens will allow their importance for the pollen-plant to be determined and, since function may be relevant to sensitisation of suceptible individuals to these allergens, these findings will stimulate the development of novel concepts in allergen prevention and therapy.Read moreRead less