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Development of food allergies

Allergic reactions to certain types of food can, in extreme cases, lead to life-threatening anaphylactic shock. People with peanut allergies are particularly at risk. Allergic reactions can also gradually develop into chronic intolerances such as coeliac disease, for example. The causes of food allergies nearly always originate in early childhood.

Food allergies can occur as a result of exposure to components contained in people’s diets. Milk products, eggs, fish, shellfish and types of corn such as wheat as well as nuts and fruit are the major causes of allergic responses. Allergic reactions include swelling of the mouth and throat area, nausea, vomiting and diarrhoea as well as itching and urticaria (nettle rash). Allergic reactions are not restricted to the gastrointestinal tract. In the worst case scenario, food allergies might lead to anaphylactic shock, a life-threatening systemic reaction leading to the failure of the cardiovascular system which requires immediate emergency treatment (injection of adrenalin).

No peanuts

Peanuts © German Ministry of Health

Such extreme reactions to food allergens are fortunately very rare. However, epidemiological studies carried out over the last few years in the USA, Great Britain and Australia, have shown that food allergy rates have increased signifanctly and are increasingly tending to provoke extreme reactions. The sensitivity to peanuts was identified as one of the most common allergies.

Peanuts contain allergens including the Ara h 2 pepide (named after the peanut's scientific name "Arachis hypogaea") and small related proteins that, upon contact with matching IgE antibodies, can trigger an allergic response within seconds or minutes after the consumption of peanuts: IgE antibodies induce an immune reaction by binding to receptors (FcεRI) on the surface of mast cells (a special type of leukocytes predominantly found in mucous membranes). Antigens induce the cross-linking of IgE antibodies. The binding of IgE antibodies to the FcεRI receptor and the aggregation of antigens leads to the activation of mast cells, which in turn leads to degranulation and the release of mediators such as histamine from the cells. The release of histamine, for example, leads to sneezing fits, itching and acute inflammation. The permeability of the blood vessels increases and the smooth muscles contract, which can lead to circulatory collapse.

Electron microscope image of a human mast cell with numerous granules. © Institute of Anatomy at the University of Rostock

An immune response that occurs as much as eight to twelve hours after exposure to a food allergen is less dramatic (also referred to as late-phase response) than the acute responses outlined above. This delayed response occurs as a result of the activated mast-cell induced synthesis of cytokines, chemokines and other mediators and is associated with the repeated contraction of the smooth muscles and the formation of oedemas. However, the delayed response to food allergens might also be a cause of severe chronic diseases such as chronic intestinal diseases or chronic asthma. The allergen-induced reaction of mast cells leads to inflammatory cells (eosinophile leukocytes and T-lymphocytes) being attracted to the reaction site during the late response phase. If the antigen is still present, allergen-specific CD-4 positive T-helper cells (TH2-lymphocytes) release cytokines (e.g. interleukin 5) that might trigger the production of eosinophile leukocytes and result in chronic inflammation.

It is very probably not just a question of chance that peanut allergies play a major role in countries where the consumption of foods containing peanuts is relatively popular both among adults and young children. In the USA and Great Britain, the number of infants that are allergic to peanuts has tripled since 1997 (around 1.4 % of all children). No data are available for Germany, but it has been shown that the incidence of food allergies has increased dramatically across the board in Germany as well as in other developed countries (more than 5% of infants and at least 2% of adults suffer from allergies). The so-called "hygiene hypothesis" states that infants brought up in extremely hygienic conditions have a lack of early exposure to infectious agents and pathogens, which is actually necessary for the development of an effective immune system (see article "Why does country air make children healthier?").

Peanut allergies are virtually unknown in developing countries where peanuts are a staple foodstuff (for example in the Sahel Zone in Africa). This could also be due to the fact that these countries are confronted with other, more immanent disease problems due to the completely insufficient disease treatment options available. 

Peanut allergy therapy in sight

It is important to point out that anaphylactic shock is very rare among people with allergies. However, the danger is sufficiently present (USA estimates anticipate 50 – 500 deaths per year as a result of peanut allergies), which is why peanut-sensitive people are well advised to avoid peanut-containing foods. Intensive research is focusing on ways of protecting people against such extreme allergic responses.

Immunotherapy is not available for people suffering from food allergies. People who are hypersensitive to insect bites (bee and wasp stings) can be “hyposensitised” or “desensitised” (by way of repeated subcutaneous injections of gradually increasing venom allergen quantities). Immunotherapy has not yet been used to prevent the onset of peanut allergies because of the danger of anaphylactic reactions occurring. A study published in November 2010 has led to hopes that effective treatment for the often-lethal peanut allergy will become available. Australian scientists identified dominant sequence fragments on the Ara h 2 allergen that are required for binding to CD4-positive T-cells and showed that they interacted with the immune cells of allergic individuals, building tolerance rather than triggering anaphylaxis. These peanut proteins seem to be excellent candidates for a peanut allergy vaccine because they do not bind to IgE antibodies and hence do not trigger anaphylactic responses. The researchers anticipate that they will be able to carry out a clinical study to test the effectiveness of the vaccine within the next three years.

The immune system develops after birth

Most food allergies have a less dramatic outcome than a hypersensitivity to peanuts. They usually develop quite slowly and the symptoms are barely recognisable. Over time, people can become sensitive to food that they once tolerated well. Well-known examples of such allergies are coeliac disease, an autoimmune disorder of the small intestine caused by a reaction to gluten (proteins in wheat and other corn), and an allergy caused by a reaction to cow’s milk protein. How do such intolerances to normally harmless foodstuff develop?

Although many details of how allergies to foods develop are not yet known, there is general agreement on the basic principles of how such allergies develop. Whether the body becomes immunotolerant or sensitive to allergens that are taken up with the food is decided in the very first few days after birth. An unborn baby grows in a germ-free environment and is then exposed to microorganisms and other antigens that stimulate the baby’s immature immune system during delivery. The maturation of the infantile immune system after birth is closely associated with the development of its digestive system that is gradually becoming exposed to environmental influences. A baby receives a reserve of antibodies (class G immunoglobulins, IgG) from its mother enabling it to fend off harmful foreign antigens during the very first phase of life. IgGs enter the blood of the unborn child by way of the placenta. In the intestine, where the infant’s immune system is exposed to very large numbers of foreign antigens taken up with the milk it is fed with, specific secretory IgA antibodies (sIgA) represent the most important line of defence against harmful foreign antigens.

Breast milk is an important source of sIgA for infancts © University Children's Hospital Heidelberg

sIgAs are produced by the immune cells in the mother's breast glands and transported into the child's intestinal tract by way of the mother's milk (in particular colostrum, a form of milk produced in the first week after delivery). The antibodies are anchored to the mucus that lines the epithelial surface and protect the baby against pathogenic microorganisms or harmful substances. sIgAs (and also secretory IgMs produced by the baby itself, though to a lesser extent) also protect the infant against bacteria and harmful substances during the initial weeks of life when the protective layer of the intestinal epithelium is still quite permeable. The primary function of secreted IgAs is to separate bacteria and food antigens from the immune cells of the blood and lymph system by entrapping dietary antigens and microorganisms in the mucus (referred to as ‘immune exclusion', see article "The regulation of the intestinal immune system"), thereby preventing the translocation of bacteria and harmful substances across the epithelial barrier. Generally, the integrity of the mucous barrier is established by the sIgAs produced by the child during the first months of its life. In the second phase, larger quantities of the major components of the mature immune system, B- and T-lymphocytes and antigen-presenting cells (macrophages, dendritic cells), start to settle in the lamina propria immediately underneath the intestinal epithelium.

However, if there happens to be a delay in the development of sIgA-producing immune cells and the intestinal immune system has not yet reached full maturity, there is a greater risk that the child may develop a food allergy. Mother's milk helps the infant to establish an immunotolerance to certain food antigens in the intestine. Amongst other things, mother's milk contains antibodies against antigenic constituents of gluten, i.e. corn proteins that cause coeliac disease. Coeliac disease is less frequent in breast-fed children than in formula-fed children. It appears that the development of a child's immunotolerance also depends on the mother's condition as studies have shown that breast-fed children tend to develop an allergy to cow's milk if their mother only has low concentrations of antibodies against cow proteins.

Publication:
Prickett SR, Voskamp AL, Dacumos-Hill A, Symons K, Rolland JM, O'Hehir E: "Ara h 2 peptides containing dominant CD4+ T-cell epitopes: Candidates for a peanut allergy therapeutic". J Allergy Clin Immunol, publ online 19 Nov 2010.
 
Further information:
Dr. Ernst-Dieter Jarasch
BioRegion Rhein-Neckar-Dreieck e.V.
E-mail: jarasch(at)bioregion-rnd.de
Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/development-of-food-allergies