4. Overview of Food Allergies

Food allergies are adverse reactions to an otherwise harmless food or food component that involves an abnormal response of the body’s immune system to specific protein(s) in foods. True food allergies may involve several types of immunological responses (Sampson and Burks, 1996). The most common type of food allergy is mediated by allergen-specific immunoglobulin E (IgE) antibodies^[1]. IgE-mediated reactions are known as immediate hypersensitivity reactions because symptoms occur within minutes to a few hours after ingestion of the offending food. IgE-mediated reactions may occur to pollens, mould spores, animal danders, insect venoms and other environmental stimuli as well as foods. IgE-mediated reactions affect perhaps 10-25% of the population in developed countries (Mekori, 1996), although food allergies represent a small fraction of all allergic diseases. Infants and young children are more commonly affected by IgE-mediated food allergies than adults; the prevalence among infants under the age of 3 may be as high as 5-8% (Bock, 1987; Sampson, 1990a; European Commission, 1998).

True food allergies also encompass delayed hypersensitivity reactions whose mechanisms are less clear. Such reactions include cell-mediated reactions that involve sensitised lymphocytes in tissues rather than antibodies (Sampson, 1990b). In cell-mediated reactions, the onset of symptoms occurs more than 8 hours after ingestion of the offending food. The overall prevalence of food-induced, cell-mediated reactions remains uncertain (Burks and Sampson, 1993), but these reactions are well documented in infants. Delayed, food-induced enteropathy has been observed in infants on exposure to milk, soybeans, and less frequently, other proteins. The most common cell-mediated hypersensitivity reaction affecting all age groups of the population is celiac disease, also known as gluten-sensitive enteropathy. Celiac disease affects 1 in every 300 to 3000 individuals in the population depending upon the specific geographic region.

Food allergies are caused by a wide variety of foods. The Codex Committee on Food Labelling established, after considerable debate, a list of the most common allergenic foods associated with IgE-mediated reactions on a -worldwide basis that includes peanuts, soybeans, milk, eggs, fish, crustacea, wheat, and tree nuts. This list was presented to the Codex Alimentarius Commission and adopted in 1999 at its 23^rd Session. These commonly allergenic foods account for over 90% of all moderate to severe allergic reactions to foods, although an extensive literature search has revealed more that 160 foods associated with sporadic allergic reactions (Hefle et al., 1996). Theoretically, any food that contains protein would be capable of eliciting an allergic reaction, although foods vary widely in their likelihood of provoking allergic sensitisation. In addition to the Codex list, allergic reactions to fresh fruits and vegetables, associated with the oral allergy syndrome (OAS), are also rather common (Ortolani et al., 1988). These foods are not included in the Codex list. The symptoms are typically mild and mostly confined to the oropharyngeal region. Some of the most significant allergens from these foods are unstable to heating and digestion. However, OAS in patients allergic to fruits and vegetables may, in some individuals, be followed by a systemic reaction (Ballmer-Weber et al., 2000). The list established by the Codex Committee on Food Labelling also includes gluten-containing cereals (wheat, rye, barley, oats and spelt) that are implicated in the aetiology of gluten-sensitive enteropathy.

In IgE-mediated food allergies, exposure to a specific food and the proteins contained therein elicits the development of food allergen-specific IgE antibodies. These IgE antibodies attach to the surfaces of mast cells and basophils, thus sensitising the individual to react upon subsequent exposure to the specific food. Thus, to become sensitised, individuals must first be exposed to the food in question. Some food proteins are more likely than others to elicit allergic sensitisation. Very limited information exists on the levels of exposure to a food that are minimally necessary to elicit allergic sensitisation in susceptible individuals. However, infants are much more likely to be sensitised than adults and are possibly sensitised to comparatively low levels of exposure to the offending food. Subsequent exposure of a sensitised individual to the offending food will likely elicit an allergic reaction. The allergen cross-links IgE antibodies on the surfaces of mast cells or basophils triggering the release of various mediators of the allergic reaction. These mediators are released into the tissues and blood, interacting with various receptors that provoke the symptoms characteristic of allergic reactions. The amount of exposure to an ingested, allergenic food protein needed to elicit a discernable reaction in already sensitised and highly sensitive individuals is not precisely known but appears to be in the microgram to low milligram range.

The manifestations of IgE-mediated food allergies range from mild to severe to life-threatening events. Individuals display different thresholds for elicitation of a reaction following ingestion of the offending food. However, the most sensitive food-allergic individuals will experience reactions from exposure to microgram to low milligram quantities or perhaps less of the offending food (limited studies have been conducted on threshold doses so the lowest-observed adverse effect level cannot be deduced precisely for any given allergenic food). Severe reactions can take place after intake of minute amounts of the offending food, and a safe threshold level below which reactions will not occur has not been defined.

Gluten-sensitive enteropathy or celiac disease is a T cell-mediated immunological response triggered by gluten (gliadin) which affects genetically disposed individuals. The active phase of the disease consists of an inflammatory process in the small intestine leading to malabsorption with body wasting, anaemia, diarrhoea, and bone pain along with other symptoms. The disease demands lifelong avoidance of gluten from wheat, rye, barley, and related cereals.

Celiac disease and other enteropathies, although recognized by this Consultation as important medical conditions, were not included in the assessment strategies considered by this Consultation.

Both IgE-mediated food allergies and non-IgE-mediated reactions are treated with specific avoidance diets. Since in both cases, the threshold dose is low and not precisely defined, affected individuals can experience difficulties in the adherence to the avoidance diets.

Almost all food allergens are proteins, although the possibility exists that other food components may act as haptens^[2]. While some food allergens have been identified and characterized, many others remain unknown. Many of the known food allergens fall into certain classes of proteins which may aid in the identification of unknown allergens from other sources. Similarly, prolamin proteins from wheat, rye, barley, etc. are involved in the elicitation of gluten-sensitive enteropathy. While the crops from which staple foods are derived contain thousands of different proteins, relatively few are allergenic. The distribution of these proteins varies in different parts of the plant and can be influenced by environmental factors such as climate and disease stress.

Conventional breeding introduces additional protein diversity into the food supply. However, variations in the protein composition of our diets brought about through conventional crop improvement practices have had little, if any, effect on the allergenic potential of our major foods. In contrast, altered dietary preferences and changes in food manufacturing and food formulation practices can have significant implications for the development of food allergies. For example, allergy to peanut (groundnut) occurs at a significant frequency in North America and Western Europe but not in other countries where peanuts are less commonly eaten. Also, recent food introductions such as kiwi fruit have proven to be additional sources of food allergens. With respect to food formulations, the wider distribution of certain ethnic foods, such as those containing sesame seeds, may contribute to increases in allergic sensitivity to certain foods. These observations provide confidence that there are not a large number of potential allergens in the food supply, but show that new allergenic foods are sometimes introduced into the marketplace.

Because of the above, a clear need exists to pay particular attention to allergenicity when assessing the safety of foods produced through genetic modification. In the assessment of the allergenicity of genetically modified foods, the characteristics of the novel gene products (proteins) must be evaluated in light of their similarities to known food and environmental allergens. In addition, if an examination of the genetically modified food in comparison to its conventional counterpart reveals the presence of any unintended, new proteins resulting from the transformation events, these unintended, new proteins should also be assessed for their possible allergenicity using a similar approach.