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Allergies and IgE

What’s an allergy and how we test

Allergy or Intolerance?

An allergic reaction is the body’s immune system responding to what would usually be considered a harmless substance in an aggressive manner. We test raised IgE levels to determine allergies.

The body perceives these substances as a ‘threat’ and produces an inappropriate response, which invokes symptoms. These symptoms usually start within a few minutes but can begin as late as two hours later.

In contrast, a food intolerance (Igg4) is a difficulty digesting certain foods and experiencing physical symptoms as a result of eating them with signs emerging hours to days later.

What is an allergy?

An allergy is a type I hypersensitivity meaning that exposure to an allergen results in the production of immunoglobulin E (IgE) antibodies, the release of histamine and symptoms.

The effect is known as an IgE-mediated immune response with symptoms occurring rapidly after (up to a few hours) an item is ingested, inhaled or touched.

Allergens are usually easy to identify due to the quick nature of the reaction within the body, however this does depend on the severity of reaction as well as other factors such as hydration, time of year and sometimes even the processing level of a food.

Many people know an allergic response to a food or non-food item has the potential to be life-threatening. In the case of severe allergy, even the tiniest traces of an allergen will have an effect on the body and will trigger an immune system response. This is because the immune system attacks a particular protein as though it could be a harmful pathogen.

Depending upon the type of item ingested and the individual, the symptoms will present themselves differently. They can appear in the form of skin rashes, hives, vomiting immediately after ingesting food, wheezing, coughing, nausea and even the swelling of mouth, throat and tongue. An individual with multiple allergies may also have different symptoms to different items.

If diagnosed with food allergies you should do your best to consistently avoid these items and in particular if you have severe allergies or asthma. It is important to note that type I allergies are a lot less common than intolerances and sensitivities but can be life-threatening in some individuals.

Why IgE?

We test your sample for allergy reactions using an in-vitro testing system which measures a raised IgE antibody reaction. On arrival at our laboratory, our technicians collate the samples and extract analytes from the dried blood spots after reconstituting the blood.  Your processed sample is then exposed to a panel of food and environmental allergen items. If a reaction is recorded during the testing, your results will be classed as positive, and indicate an allergy which will be documented on your results.

The response of the antibody to an item is an indictor of an allergy symptom. These reactions can vary significantly and present in your body through tissue or organs, which in turn leaves to discomfort, pain, and in some cases, damage. Your results and the data contained within them can be used to consult with your GP, specialist or immunologist.

There are a wide number of scientific studies that support the link between raised IgE levels and allergies which are available both online and through scientific journals. We have provided summarised copies of published articles related to this field.

Scientific studies:

Ramona A. Hoh et al. Origins and clonal convergence of gastrointestinal IgE+ B cells in human peanut allergy, Science Immunology (2020)

B cells in human food allergy have been studied predominantly in the blood. Little is known about IgE+ B cells or plasma cells in tissues exposed to dietary antigens. We characterized IgE+ clones in blood, stomach, duodenum, and esophagus of 19 peanut-allergic patients, using high-throughput DNA sequencing. IgE+ cells in allergic patients are enriched in stomach and duodenum, and have a plasma cell phenotype. Clonally related IgE+ and non-IgE–expressing cell frequencies in tissues suggest local isotype switching, including transitions between IgA and IgE isotypes. Highly similar antibody sequences specific for peanut allergen Ara h 2 are shared between patients, indicating that common immunoglobulin genetic rearrangements may contribute to pathogenesis. These data define the gastrointestinal tract as a reservoir of IgE+ B lineage cells in food allergy.

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Food Allergy – Alessandro Fiocchi, MD and Vincenzo Fierro, MD (2017 WHO)

…The definitions and concepts of allergic and hypersensitivity conditions beyond the allergy community have often created misunderstanding. For an optimal clarification:

  • the term “atopy” is used when individuals have an IgE sensitization as documented by IgE antibodies in serum or by a positive skin prick test;
  • “hypersensitivity” is defined as “conditions clinically resembling allergy that cause objectively reproducible symptoms or signs, initiated by exposure to a defined stimulus at a dose tolerated by normal subjects”, and
  • “allergy” is defined “a hypersensitivity reaction initiated by proven or strongly suspected immunologic mechanisms”…

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IgE in Clinical Allergy and Allergy Diagnosis 

…A fairly good knowledge exists about the various steps in the allergic reaction, but despite present knowledge, the prevalence of allergic diseases is still increasing. In some areas of the industrialized world up to 50% of the population is affected. More efforts must be dedicated to the understanding of allergic sensitization and how it can be prevented. The identification of the pathological role of IgE and the subsequent release of inflammatory mediators and cytokines has enabled physicians to treat allergic symptoms with regard to the underlying immunological mechanisms. New pharmacotherapy in the form of a humanized monoclonal anti-IgE antibody designed to eliminate IgE may have a valuable role in treating IgE sensitized individuals.
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Quantitative IgE antibody assays in allergic diseases

…During the past several years, immunoassays for specific IgE antibodies have been refined to permit reporting results in mass units. Thus quantitative immunoassays for IgE antibodies may be an adjunct to skin tests. In cases of food allergy among children with atopic dermatitis, cutoff values for IgE antibody concentrations to egg, milk, peanut, and fish have been derived to provide 95% positive and 90% negative predictive values. Food-specific IgE antibody determinations can also be used to predict which food allergies are resolving spontaneously…

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Utility of food-specific IgE concentrations in predicting symptomatic food allergy 

…One hundred children (62% male; median age, 3.8 years; range, 0.4-14.3 years) were evaluated for food allergy. The diagnosis of food allergy was established by means of history or oral food challenge. On the basis of the previously established 95% predictive decision points for egg, milk, peanut, and fish allergy, greater than 95% of food allergies diagnosed in this prospective study were correctly identified by quantifying serum food-specific IgE concentrations…
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A follow‐up study of children with food allergy. Clinical course in relation to serum IgE‐ and IgG‐antibody levels to milk, egg and fish 

Eighty‐two children with food sensitivity were followed‐up for 2‐5 years. Most children showed a decreasing sensitivity and the clinical course of food allergy seemed to reflect the course of the humoral immune responses to the offending foods. The occurrence of IgE‐ and IgG‐antibodies parallelled in most cases. However, an early, high IgG/IgE food antibody ratio seemed to be a good prognostic sign, indicating a possible blocking capacity of IgG‐antibodies.
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Understanding allergies

The classification of allergic and hypersensitivity diseases, which were defined by the European Academy of Allergy and Clinical Immunology (EAACI) and the World Allergy Organization (WAO) provides a clear definition.

According to the WAO, the correct diagnosis of an allergy is if specific conditions are met, including; a compatible clinical history, and positivity to in vivo and/or in vitro tests (IgE blood test or skin prick test) to prove underlying mechanism and aetiology, meaning to be classified as allergic to an item there is a need for a positive test result as well as symptoms.

Allergies are the most common chronic disease throughout Europe. According to the EAACI, up to 20% of people with allergies struggle daily with the fear of a possible asthma attack or anaphylactic shock. It can be life-threatening.

There are a variety of environmental influences and genetic factors of the body, which underly the immunopathogenesis of food allergy and its manifestations. There have been some clinical studies, which have altered many people’s understanding of what causes a food allergy.

Overall, food allergies are a chronic condition and can be hereditary. However, there has been a recent rise in women developing specific food allergies and allergic rhinitis during the menopause.

Allergies Science

For an allergy to exist, allergen sensitisation must first occur. Antigen-presenting cells, including macrophages and dendritic cells, are responsible for detecting the allergen. This can happen in a variety of ways, including inhalation via the nose and lungs, as well as through the skin and the gastrointestinal tract.

When cells containing an antigen interact with an allergen, it is perceived to be an invader, even though we wouldn’t normally consider the substance harmful. Subsequently, the allergen is then absorbed into the antigen-presenting cell, processed and then displayed on the surface of the cell.

Next, the cell then migrates and presents the allergen. This process stimulates the B-cell and produces antibodies specific to the allergen. From here, these particular antibodies, (IgE) are then released and can attach themselves to receptors on various surfaces of other cells in the mucosal surfaces and on subsequent basophils contained within the blood.

There is a period of sensitisation, and afterwards comes a period of latency, then on subsequent re-exposure to the allergen, the allergic response is triggered. In this process, an allergen can connect with the IgE on the surfaces of the mast cell, and this causes the cell to release nasty and inflammatory cell mediators. These include histamines and other mediators, all of which act differently and create a variety of symptoms in different organs.

The key to fully defining allergy pathogenesis and developing novel therapeutic possibilities may be in further understanding the gut microbiome and advancing research into epigenetics.

Prince, B.T; Mandel, M.J; Nadeau, K; Singh, A.M. Gut Microbiome and the Development of Food Allergy and Allergic Disease. Pediatric Clinics of North America. 2015;62:1479-92 Xie, J; Lotoski L.C; Chooniedass, R; et al. Elevated antigen-driven IL-9 responses are prominent in peanut allergic humans. PLoS One. 2012;7(10):e45377 Nursing Times. (2006). The pathophysiology of allergic responses.

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