The University of Southampton has been a strong centre for allergy research for many years, and our Southampton Allergy Centre is recognised as the World Allergy Organization Centre of Excellence for allergy research, clinical service and education. Our work covers a wide range of allergies, including asthma, allergic rhinitis (hay fever), food allergy and eczema.
One in five people in developed countries such as the UK and Australia suffer from an allergy at some point in their lives – and allergies are on the rise. Southampton researchers are leading the largest study of its kind to improve our understanding of allergies, and through our MSc Allergy programme, we are developing the experts of the future.
By studying the genetics of allergies, researchers can predict who might develop the condition, and understand more about the biology of the disease, which could lead to new therapies in the future. Professor John Holloway’s team focuses on epigenetics: chemical changes to the DNA that don’t involve a change in the sequence of the DNA code.
“Epigenetic marks are extra messages in the DNA that control the level of gene expression,” explains John, Professor of Allergy and Respiratory Genetics, and Associate Dean, Research for Medicine at Southampton. “The fascinating thing about them is that they can be added to your DNA in response to an environmental exposure. It could be your mother’s diet while she was pregnant with you, it could be cigarette smoke in the air, which could lead to a chemical change in your DNA that changes the way genes are expressed, and that might increase your risk of disease.”
Through this study, we concluded for the first time that peanut allergy is increasing – and our research has been quoted in many guidelines to show that peanut allergy is on the rise.
Isle of Wight allergy study
A Southampton research team has been studying a particular epigenetic mark, DNA methylation, in the world’s longest-running study following people with allergies from birth.
“We designed this study to assess the prevalence and natural history and the risk factors for the development of asthma and allergy, to first assess the burden of disease in the community and devise preventative strategies,” says study leader Hasan Arshad, Professor of Allergy and Clinical Immunology at Southampton, and Director of the David Hide Asthma and Allergy Research Centre, Isle of Wight.
All 1,536 participants of the study were born in 1989 on the Isle of Wight, UK. Every child who was born during a 14-month period on the island was recruited to this study to make it a representative population sample. The researchers then followed them up at ages one, two, four 10, 18 – and they are currently being seen again at age 27. “Our aim is to understand how allergies develop, and this study is the ideal way to do this because allergies develop early in life and they can change over time,” explains Hasan. “Children often develop eczema, then asthma, then hay fever, sometimes all together or sometimes one disease improves and another appears. Through this study we are shedding light on why this happens.”
The study is clinical as well as lab-based. When the children were still in infancy, the researchers used detailed questionnaire assessments to find out how many children develop allergies and what factors influence this. “We asked the parents whether their children have allergy symptoms – wheezing, reacting to foods, itchy skin, runny noses and so on,” says Hasan. “We also asked about any other factors in their lives that could be contributing, such as pets in the house, whether the child was delivered by caesarean, breastfed or bottlefed, and if the parents themselves have a history of allergies.”
The researchers also collected blood from the umbilical cord of every baby at birth to measure levels of allergy antibodies and determine whether high levels of these antibodies could predict the risk of developing allergies in later life. “We found that having allergy antibodies in the cord blood at birth is not a good predictor for developing allergies in the future. This was a useful result because back in the 1990s this test was starting to be done on children, and we were able to provide evidence that this was not a good test and should not be done.”
The team also carried out a number of clinical tests at various points during the participants’ childhood, including skin tests, lung function tests and measuring inflammation markers such as the amount of nitric oxide in their airways or cytokines in their blood.
Looking at about 400 genes, the team has identified new genes related to asthma. However, genes are only one part of the puzzle, explains Hasan: “We can be born with the genetic susceptibility for many diseases, such as cancer or asthma, but not everyone with this susceptibility will develop the disease. Take lung cancer, for example: there are some genes that make us susceptible to that risk, but if you smoke you multiply that risk whereas if you don’t smoke, the risk of developing lung cancer remains very low.”
By looking at the epigenetic markers, the team can predict who is most likely to develop asthma and the environmental factors that are most likely to influence the gene. This type of research relies on a multidisciplinary team, including clinicians, biomedical scientists, biomathematicians and epidemiologists. The study also involved collaborations across the world with universities and industry. “Working with business is important because we can help each other in the process of taking a discovery through to a new treatment that will impact on patients,” says John.
Working with business is important because we can help each other in the process of taking a discovery through to a new treatment that will impact on patients.
The Isle of Wight study has been a focus of Southampton allergy research for the past 20 years and has generated over 100 research papers that have contributed to understanding of the natural history of allergic disease – that is, how asthma develops, how it improves in some children, and what are the factors that favour improvement and what are the factors that increases risk.
“Through this study, we concluded for the first time that peanut allergy is increasing – and our research has been quoted in many guidelines to show that peanut allergy is on the rise,” says Hasan. The researchers also developed a scoring system to show the risks of individual children who have a wheeze of going on to develop asthma.
The study has also revealed a gender bias in the inheritance of allergies: if the mother has asthma, a daughter has more chance of developing asthma than a son. “This is important from a practical point of view, as it will help tell us who is at most risk for allergies in the family.
Through our Respiratory Biomedical Research Unit, funded by the National Institute for Health Research, we have strong links with the University Hospital Southampton NHS Foundation Trust to carry out innovative bench-to-bedside research. This has led to new treatments, including a monoclonal antibody therapy that is now available to patients with severe asthma. It has also led to the spin-out of drug development and discovery company, Synairgen.
Our research has also translated into policy. Southampton researchers were part of a team that found that introducing peanut into an infant’s diet within the first 11 months of life can prevent peanut allergy in those at high risk. Graham Roberts, a professor of allergy and respiratory medicine, says: “For many years, guidelines and paediatricians have recommended that infants avoid peanuts. However, this study shows that early, sustained consumption of peanut is safe and results in a substantial and significant reduction in the development of peanut allergy in high-risk infants by five years of age.”