Allergic disorders includes asthma, eczema (atopic dermatitis), allergic rhinitis and food allergy. They have increased in prevalence in recent decades and now affect up to one in three adults and one in two children in economically developed countries. Our research programme covers all ages and integrates epidemiology, basic science and clinical trials to answer key questions raised by the increasing prevalence of allergic diseases.
A major aim of our research programme is to understand why so many children develop asthma and allergy, focusing on early life factors, both antenatal and postnatal. We are looking at both genetic and environmental factors and how epigenetic mechanisms plays a role in modifying the risk of allergic disease, in order to determine how we might reverse this process. Our Group is also developing interventions to both prevent and treat asthma and allergic disease in childhood. We are working with a number of other groups within University of Southampton and with academic institutions across Europe and the US to deliver this programme.
Projects :
Southampton Women’s Survey Children’s Cohort ( Graham Roberts , John Holloway , Jane Lucas , Judith Holloway , Katy Pike ) Working with the MRC Life Course Epidemiology Unit, The Paediatric Allergy and Respiratory Group have utilised prospectively collected data to understand how nutrition and growth antenatally and postnatally impact on the development of asthma and allergy in childhood.
The impact of food allergy on quality of life in children and young people ( Jane Lucas , Graham Roberts , Judith Holloway ): The Paediatric Allergy and Respiratory Group have investigated the impact of food allergy on quality of life and daily tasks such as shopping and eating out, using mixed methods including qualitative interviews, recording participant tasks and validation and use of questionnaires in food allergic patients. The research is now focusing on interventions to improve quality of life and management of these patients.
EuroPrevall Food Allergy Project – Birth Cohort ( Graham Roberts , Kate Grimshaw and Erin Oliver ) Funded by European Union’s FP6 programme, this large pan European birth cohort is providing an exciting insight into the early origins of food allergy in childhood.
Natural history and risk factors for asthma and allergy : ( Hasan Arshad , Graham Roberts , Ramesh Kurukulaaratchy ). With the David Hide Asthma and Allergy Research Centre at St Mary’s Hospital in the Isle of Wight, we are investigating the development of allergic disease using longitudinal cohorts recruited at birth who have now reached adolescence and adulthood.
Genetics of allergic disease ( John Holloway , Hasan Arshad , Graham Roberts , Jane Lucas , Michael Arden-Jones , Peter Howarth ) Working with local cohorts (The Isle of Wight Birth Cohort, Southampton Women’s Survey, Southampton Family cohort) in addition to external collaborators both nationally and internationally we are undertaking a number of studies into the genetic basis of allergic diseases, focusing on gene-environment interactions in the early life origins of asthma.
Transgenerational epigenetic inheritance of allergy in a multigenerational cohort ( Hasan Arshad , John Holloway , Graham Roberts , Ramesh Kurukulaaratchy ): In partnership with Professor Wilfried Karmaus and Dr. Hongmei Zhang (University of South Carolina), and Professor Susan Ewart (Michigan State University), we are examining genome-wide DNA methylation in women of the Isle of Wight longitudinal birth cohort, based at the David Hide Asthma and Allergy Research Centre , and are recruiting their children as the second generation in this cohort.
Primary prevention of allergic disease : ( Hasan Arshad , Graham Roberts , Ramesh Kurukulaaratchy ). In conjunction with the David Hide Asthma and Allergy Research Centre at St Mary’s Hospital in the Isle of Wight, we are investigating various strategies to prevent the development of allergic disorders. In a National Institute of Health Research (NIHR) funded study, we are looking at the impact of early life intervention, using allergen avoidance measures during infancy, on the development of asthma and allergy in young adults. In a second study within the Respiratory BRU, we ( Hasan Arshad , Graham Roberts , Ramesh Kurukulaaratchy, Ratko Djukanovic ) are assessing whether allergen sublingual immunotherapy with a house dust mite preparation will prevent the early onset of allergy and the later development of childhood asthma in children at high risk of allergy.
Asthma across the life course : ( Stephen Holgate , Donna Davies , Graham Roberts , Hasan Arshad , Peter Howarth , Hans Michael Haitchi ): This includes a number of interconnected projects: (1) We are investigating the pathophysiology of viral-induced exacerbations of asthma in children, using an ex-vivo system with brushing samples collected from the airway. This work is now being extended to understand how viruses may be involved in the early pathogenesis of asthma in childhood. (2) We are also using biopsy and brushings from well phenotyped cohort subjects to understand why some children grow out of asthma during adolescence while others have more persistent disease.
Early proof of efficacy trial of IFN-β in childhood asthma : ( Graham Roberts , Ratko Djukanovic , Donna Davies ): This work is part of the Respiratory BRU portfolio, where we wish to establish proof of efficacy of nebulised interferon beta as a preventative therapy to prevent viral exacerbations of asthma in childhood.
Specific IgE to recombinant major allergen protein in the diagnosis brazil nut allergy ( Hasan Arshad , Anthony Williams ): This study aimed to improve the diagnosis of brazil nut allergy using recently available technology of component resolved diagnostics.
Food Allergy and Intolerance Research : ( Hasan Arshad , Graham Roberts ): In collaboration with Prof. Taraneh Dean and Dr. Carina Venter of Portsmouth University and the David Hide Centre on the Isle of Wight, we are investigating prevalence and natural history of food allergy in 10 year olds, who have been assessed in early childhood. Dr. Venter is supported by National Institute of Health Research and the original study was funded by Food Standard Agency.
Biomarkers of Acute Allergic Reactions : ( Andrew Walls , Jane Lucas , Efrem Eren ): Research is focused on the investigation of new biomarkers for acute allergic reactions, examining, in particular, the levels of products of mast cell and basophil activation in the circulation, saliva, sputum and other biological fluids. Sensitive assays have been developed for mast cell carboxypeptidase, chymase and dipeptidyl peptidase I (DPPI) as well as for tryptase. Levels of these mast cell proteases are increased following acute allergic reactions to foods, drugs and insect stings, and high baseline levels may be associated with the risk of serious reactions. Our production of basophil specific monoclonal antibodies has allowed the identification and characterisation of a unique biomarker for basophils, termed basogranulin, which allows investigation for the first time of the extent of basophil activation in clinical allergy.
Mediators of Inflammation : ( Andrew Walls , Tony Sampson , Tim Millar , Jane Warner ): The application of cellular and molecular approaches for the investigation of fundamental processes in allergic disease is well established. Studies of the mediator actions of mast cell proteases have established that they are valuable not only as clinical markers, but also as key mediators of allergic inflammation and tissue remodelling. Tryptase and chymase have received particular attention and have become targets for therapeutic intervention, as has DPPI. The means by which these proteases can profoundly alter the behaviour of various cell types is unclear but could involve activation of protease activated receptors, a separate line of investigation. Other mediators under investigation are the eicosanoids, including leukotrienes, prostanoids and anti-inflammatory lipids (lipoxins, resolvins), and their roles in allergic conditions of the lungs, gut and skin are being explored.
The role of Staphylococcus aureus in atopic eczema pathogenesis
:
(Michael Ardern-Jones
,
Marta Polak
, Stuart Clarke, Luanne Stoodley-Hall
)
Atopic eczema has long been recognised to be predisposed to infection by S. aureus. However, whether the S. aureus plays an active role in disease pathogenesis or is an opportunistic organism remains to be determined. We (Ardern-Jones, Polak) have developed an immunocompetent in vitro model of the skin and are using staphylococcal isolates from atopic eczema to stud the mechanism of microbe induced skin inflammation (
Ardern-Jones
, Polak
). We will also use this model to examine the propensity of staphylococcus to form biofilms on skin ((
Ardern-Jones
, Polak, Stoodley-Hall
). Funders: British Skin Foundation.
We have a cohort of atopic eczema patients and this project will analyse the Staphylococcal isolates isolated from different body sites for markers of virulence and superantigen production ((
Ardern-Jones
, Clarke
). These will be compared to control isolates from healthy individuals (
Clarke
). Funder: Health protection Agency
Development of novel diagnostic assays in severe cutaneous drug allergy reactions
: (
Michael Ardern-Jones
, Marta Polak
)
Drug allergy reactions are common and occasionally fatal. Dermatologists are often the first to identify these potentially severe systemic reactions because of the early involvement of the skin. Drug patch testing is only undertaken after the clinical problem has resolved and the lymphocyte proliferation assay (LPA) takes one week to perform; thus neither of these investigations contributes to management in the acute stages. We have demonstrated that ELISpot assay of drug stimulated expression of IL-4 and IFN-g is a rapid, sensitive and convenient diagnostic test for drug allergy. Further development of these rapid non-radioactive in vitro assays for routine use will provide a significant advancement in our management of patients suffering from drug reactions.