Allergic Reactions to Food

Clinical Significance: The term allergy was originally defined by Clemens von Pirquet to mean the body’s increased ability to react to a foreign substance. Today the term allergy means an oversensitivity to foreign substances which are normally harmless. Alongside any genetic predisposition, numerous non-genetic factors also play a role, such as exposure to the allergen, nutritional condition, existing chronic diseases and acute viral infections. Atopy is a hereditary disposition to developing allergic reactions such as allergic asthma, rhinitis (hay fever) or dermatitis (including atopic eczema).

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The most frequently occurring allergy is a type I hypersensitivity reaction, in which specific IgE anti- bodies are formed. The symptoms (rash, oedema or itching) generally occur shortly after contact with the allergen. These allergies are therefore also termed immediate type reactions. Allergens are acquired either through the air and mucous membranes of the body (inhalation allergies) or by ingestion (food allergies).

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More than 15% of the population in industrial countries suffer from an immediate-type allergy. Typical allergic reactions are rhinitis, conjunctivitis and allergic asthma. A worldwide increase in allergic rhinitis has been observed, with a prevalence of 4% to more than 40% in various regions. Inhalation allergies can be triggered by seasonal allergens (pollen from trees, grasses and weeds) or all-year-round indoor allergens (house dust mites, domestic animals, mould spores). The allergic symptoms intensify with every further exposure to the allergen. If a systemic allergic reaction occurs, serious, even life- threatening reactions can result (anaphylactic shock).

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A food allergy is an IgE mediated reaction which leads to symptoms within hours of having ingested the food. The most common foods causing allergic reactions are peanuts, soy, wheat, shellfish, fish, milk, eggs and tree nuts. Possible symptoms are burning or itching in the oral cavity, nausea, gastrointestinal spasms, diarrhoea and skin rashes. Severe reactions can also lead to asthma attacks, breathlessness, increased heart rate and to panic attacks and confusion. In rare cases anaphylaxis can occur (e.g. after the consumption of peanuts, nuts or fish).

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However, allergic reactions to foods of plant origin can also be caused by cross-reacting IgE antibodies. These reactions, termed cross-allergies, are based on the structural similarity between proteins which are present in both the food as well as in the corresponding inhalation allergens of plant origin. For example, patients with a birch pollen allergy can also develop allergic reactions to apple, celery, hazelnut, potato or kiwi.

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Immunotherapy or hyposensitisation (desensitisation) established as a treatment for type I allergy does not provoke a change in IgE levels, although a significant reduction of the symptoms can be achieved. A definite response of a patient to immunotherapy normally manifests as an increase in the allergen- specific IgG antibody concentration during the course of treatment. However, this does not always correlate with a remission in symptoms.

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Many allergens are glycoproteins and contain oligosaccharide side chains which are bound to the protein framework of the allergens. Some patients develop specific antibodies against these carbo- hydrate structures. The abbreviation CCD stands for cross-reactive carbohydrate determinant. CCDs are present in many plant and animal allergens. Due to their significant similarity in structure, CCDs are known to cause a strong cross reactivity. Although the importance of specific IgE antibodies against CCDs has not yet been fully understood, they are considered to be irrelevant for diagnosis in most cases and as such complicate the interpretation of positive in vitro diagnostic results. For this reason, the presence of specific IgE antibodies against CCDs may provide useful additional information, especially when positive IgE results disagree with the clinical picture, and can serve as an interpretation aid in the evaluation of overall test results.

Cross reactions: Due to the similar structure of the allergens, e.g. similarities in chemical substances or botanical relations, cross reactions may occur. The specific IgE antibodies that have developed in a patient also attach to identical epitopes of homologous protein allergens.

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Limitations of in vitro allergy diagnostics

Accurate performance of the assays according to the test instruction will lead to reliable and reproducible results. In any case, the final diagnosis should not be solely based on one type of analysis. A well- founded anamnesis and further laboratory findings should always be taken into account. Skin tests as well as provocation test (if possible) are mandatory to receive the entire information needed for an optimal decision regarding the specific immunotherapy that should be applied. The clinical picture is not always in line with in vitro test results.

Negative in vitro results may occur e.g. when:

• symptoms are not IgE-mediated,

• samples were taken before the organism was able to produce antibodies against the antigen, - IgE concentrations reached a minimum a long time after sensitisation.

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Positive results with specific IgE in vitro tests do not necessarily have to correlate with clinical manifestations.

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Many IgE antibodies can cross-react with various allergens or redundant carbohydrate structures. Especially food allergens frequently show a negative result in vitro although clinical symptoms may be present. This phenomenon can be explained through the effect of maturing, industrial processing, cooking, or frying of the allergen. Furthermore, the allergic reaction can be induced by a metabolite of the allergen resulting from the digestive process in vivo, which cannot exactly be recapitulated by in vitro diagnostics. Above all, some food is likely to be very sensitive to the coupling procedure to the solid phase so that not all allergens which are present in the native form may be present.

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For the determination of specific IgE antibodies a variety of test systems is available. Due to the variability of the source material used for the production of allergen extracts and the manufacturing process itself the quality of the extracts used for allergy diagnostics varies significantly. Therefore the results of different test systems cannot easily be compared to each other due to the lack of international standards – neither for the allergens, nor for the antibodies used by these assays. Thus, a slight deviation between different test systems cannot be ruled out and is not a general criterion for the quality of the assay.

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In general, identical results for different patients do not necessarily mean identical clinical manifestations.

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Intended Use:

The test is used for the diagnosis of sensitisations that may lead to allergy-associated symptoms such as conjunctivitis, rhinitis or gastro-intestinal problems. The test is designed for semiquantitative in vitro determination of allergen specific IgE (sIgE) in plasma, contributing to the diagnosis of allergies.