Food Allergy: where does it begin? We are starting to understand what is going wrong in the immune system that leads to an allergic reaction to foods. Our experiments suggest that a highly specialised, dendritic cell plays a central role in the generation of an adverse reaction to food.

Dendritic cells Dendritic cells are a special type of white blood cell. They circulate throughout the body looking for foreign molecules such as infectious agents and toxins. When these cells encounter foreign molecules they capture them, and then show them to other cells of the immune system, which can then decide on a response. We looked at how dendritic cells interacted with T- cells, which can initiate an immune response. Dendritic cells from people who were non-allergic to cow’s milk when mixed with cows milk nearly all died when exposed to T- cells, whereas those from allergics survived. Small Intestinal dendritic cells do not produce appropriate levels of IL-12, a regulatory molecule in immune responses in allergy-susceptible mice compared to allergy-resistant mice.

Breakdown in regulation In allergy, there may be a breakdown of different immunoregulatory pathways used by the immune system regulate itself.

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Immunology of Allergy Food allergy is an increasing important health problem with around 3 - 5% of adults suffering severe forms. Our research focuses on understanding the cellular and molecular immunology of allergy. Exposure and transport Exposure to food allergens takes place in the gut. Specialised cells are involved in the transport of food material from the lumen to the highly developed intestinal immune system. First Contact First contact with an allergen does not evoke an allergic reaction but rather primes the immune system, defining the nature of subsequent exposures to the allergen. Peyer’s patches in the intestinal wall are important parts of the immune system. Our work suggests that a specific cell type in these patches, the dendritic cell, plays a pivotal role in committing the immune system towards a “normal”- type or “allergic”-type response. The allergic response induces the immune system to produce IgE antibodies. Subsequent Contacts IgE antibodies bind to specific molecules located on the surface of Mast cells of various tissues, especially the skin, gut and respiratory system. Subsequent exposure to the allergen provides the signals necessary for Mast cells to initiate the adverse reaction. Reaction Contact between the allergen and antibodies on the surface of Mast cells induces the release of powerful chemicals ultimately responsible for the clinical symptoms of food allergy.

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80 70

50 40 30

Selenium intake ([g/d)

60

20 10

Finland Switzerland Netherlands Belgium Denmark Slovakia Sweden France Germany UK Poland

0

Selenium and Immunity Intakes of selenium in the UK have dropped by 30-50% over the past 30 years, mainly due to the replacement of Canadian wheat (high selenium) with European wheat (low selenium). This has resulted in a fall in our plasma selenium concentrations. Selenium is involved in the maintenance of antioxidant defence systems and immune function, so one of the possible consequences of marginal selenium status is impaired immune function. Scientists at IFR have shown that selenium increases the resistance of cultured human white blood cells to influenza virus. In an FSA - funded study we are currently investigating whether increased dietary selenium improves whole body immunity. Our volunteers are eating either selenium enriched meals (made of onions fertilised with selenium), or high selenium yeast supplements. We measure the activity of their immune system in response to flu vaccination. If our results are positive, increasing selenium intake could be a useful public health strategy, not only for preventing influenza and other infectious diseases in the elderly but for prevention of chronic diseases in which the immune system is involved (e.g. certain cancers). Meat, cereals, fish, and eggs, are the main contributors to dietary selenium intake. Foods that contain high levels of selenium are offal, Brazil nuts, shell fish, meat and eggs.

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Project Partners in Europe United Kingdom Switzerland Denmark Sweden Iceland Czech Rep.

Netherlands Spain Austria Poland Bulgaria Hungary

Germany France Greece Italy Lithuania Ireland

Managing Allergens in Foods Why is food allergy such a problem? It is estimated that 5 - 7% of infants and between 1- 2% of adults suffer from some type of IgE-mediated food allergy. The symptoms happen quickly (within a couple of hours of eating a food) and can be triggered by tiny amounts of food in very sensitive individuals – for a peanut allergic child even a kiss from someone who has eaten nuts can be enough to cause a reaction! We are missing many pieces of information to help us manage food allergies more effectively. To help fill the gaps the EU have funded a €14M project called EuroPrevall which is led by IFR (www.europrevall.org).

Ghana outside Europe

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How much is too much? Cross-contamination of foods is difficult to manage in a food factory when, for example, nut-free and nut-containing products may be manufactured on common processing lines. To help the industry manage allergens in foods they need to know how much can cause a reaction. In the EuroPrevall project, we are collecting this information for several foods across Europe. The only way to find out, how much is too much, is by feeding people with food allergies a problem food in increasing amounts and seeing at what dose they react. This has to be done in a way that hides the problem food, as a reaction may be triggered in an allergic consumer just because they can smell it.

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Can we get rid of allergens in foods? It maybe possible to remove allergens from foods – one way is by selecting raw produce naturally low in allergens. Another way could be by using novel processing techniques like high pressure processing. We are using apple allergy as a model to study this. What is apple allergy? Apple allergy takes two forms, which are different in terms of their symptoms, their geographical distribution and the protein that causes them. Studying these two related allergies gives us an insight into how allergies develop and how they might eventually be controlled. Mild apple allergy occurs in people who are already allergic to birch pollen. It occurs mainly in northern Europe, symptoms including itching and swelling of the mouth and throat. It is caused by a protein molecule called ‘Mal d 1’. Similar proteins also occur in birch pollen, pear, celeriac and carrot. Consequently people with birch-pollen allergy may develop allergy to any of these foods. The Mal d 1 protein is easily destroyed by heating, so most people with this allergy can eat cooked foods and juices. Severe apple allergy is often associated with peach allergy, and tends to occur in Mediterranean countries. Symptoms include urticaria, abdominal pain, vomiting and life-threatening anaphylactic shock. The protein that causes the severe apple reaction called ‘Mal d 3’ is much tougher – it survives in many processed foods. Apple allergies around Europe More people have antibodies to the birch pollen allergen Bet v 1, and to the “mild” apple allergen Mal d 1in the Netherlands, Austria and Northern Italy but people in Spain were allergic to the “tough” allergen Mal d 3.

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A

Breeding and post-harvest storage approaches to reducing allergens in foods A number of factors influence the level of allergens in apples. For example freshly harvested fruit have low levels of the “mild” allergen Mal d 1 which increases in stored apples. Consequently some people can eat fresh but not stored apples. In contrast, levels of the tough allergen Mal d 3 are lowest in the stored apples. At present we do not know if these are safe to eat for people allergic to this “tough” allergen. In the long term, understanding these effects may help growers and processors deliver fresh foods better suited to the needs of allergic consumers.

B

The figures show the effect of storage time and cultivar (Cox, Jonagored) on A “mild” apple allergen Mal d 1 and B “tough” apple allergen Mal d 3. Novel processing approaches to reducing allergens in foods We know that if the apple allergen, Mal d 3, is heated in a particular way we can reduce its allergenic potential. Some new processing procedures, such as high pressure, may be even more effective. We are working in the newlyfunded NovelQ project to investigate this using the apple system and a related allergen in peanut.

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