Allergy & Intolerance Testing Science

Learn more about the science behind our different allergy & intolerance tests

ALLERGY TESTING

1) IgE Science

With Allergy Test, you know you’re getting the best test for you because we offer a variety of tests, designed to give you exactly what you’re looking for.

Our Allergy Test kit offers ELISA IgE blood testing, but what does this mean?

IgE antibodies are a key feature in the humoral immune response, fighting potentially dangerous antigens, which are foreign substances like bacteria, parasitic worms, and viruses that keep our body safe.

The prevalence of IgE mediated allergy food reactions has been estimated at 3-4% of all children and adults ⁽¹⁾. These dangerous, abnormal reactions are caused by food antigens and can be classified as immune IgE mediated and non IgE mediated.

The clinical manifestations or symptoms can be an anaphylactic reaction, atopic dermatitis, enterocolitis and oesophagitis. ^(2,3) These symptoms can be displayed, if it’s an intolerance, as headaches, bloating, localized itching, or skin irritations such as eczema, excessive mucous production, excessive gas, diarrhea, and fatigue.

The allergy reaction symptoms can include localized swelling (i.e., of the throat or tongue), a rash, difficulty breathing and anaphylactic shock.

IgE antibodies are involved in Type I (or Type 1) allergies and they can cause rapid type immune reactions, with symptoms occurring within a few minutes up to two hours after eating a specific food.

Allergic patients produce IgE antibodies specific for foreign antigens, which are harmless to non-allergic individuals. These antibodies bind to IgE-specific receptors on the surface of mucosal and cutaneous mast cells and circulating basophils.

IgE antibodies are located on the chromosome 14. Inhaled or ingested allergens cross-link IgE bound to these effector cells, which results in aggregation of the receptors ⁽⁴⁾.

This cross-linking and aggregation cause the immediate release of preformed mediators such as histamine and, shortly thereafter, the release of newly formed mediators such as arachidonic acid products (e.g., leukotriene D4, prostaglandin D2) and cytokines such as tumor necrosis factor-α(TNF-α), IL-4, and IL-5 ⁽⁵⁾.

In an allergic response, an allergen stimulates the release of antibodies (IgE), which attach themselves to mast cells. Following subsequent allergen exposure, the mast cells (migrant cells part of the immune system) release substances such as histamine (a chemical responsible for allergic anaphylactic symptoms) into the tissue. Food item/s responsible for allergic reactions must be avoid completely.

Is IgE Testing still what you’re looking for? Then check out the Allergy Test here.

References:

1) Macchia D, Melioli G, Pravettoni V, Nucera E, Piantanida M, et al. On behalf of the Food Allergy Study Group (ATI) of the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). Guidelines for the use and interpretation of diagnostic methods in adult food allergy. Clin Mol Allergy. 2015; 13: 27.

2) Ortolani C, Ispano M, Pastorello E, Bigi A, Ansaloni R, The oral allergy syndrome. Ann Allergy. 1988; 61: 47-52

3) Waserman S, Watson W, Food allergy. Allergy Asthma Clin Immunol 2011; 7 (1): S7.

4) Chang TW. The pharmacological basis of anti-IgE therapy. Nat Biotechnol 2000;18:157–162

5) Williams CM, Galli SJ. The diverse potential effector and immunoregulatory roles of mast cells in allergic disease. J Allergy Clin Immunol 2000;105:847–859

More information about the IgE antibodies structure and clinical translation:

INTOLERANCE TESTING

2) IgG4 Science

At Allergy Test, we offer a range of blood tests to help find the right test for you. Our Intolerance Test kit offers an IgG4 ELISA blood test, but what does this mean?

The IgG4 antibodies can influence the inflammatory response but not activate it. We are using IgG4 in our intolerance tests because we are investigating delayed symptoms that could be associated with food and non-food intolerances.

These do not cause an immediate immunological response, however, could still be causing you problems. For food intolerance, the presence of specific IgE and IgG antibodies can be observed. Some subclasses of IgG (mainly IgG4) inhibit the degranulation of basophils and mast cells and the activation of the complement cascade.

We are using IgG4 antibodies because, when we are testing intolerances, we are not looking at the immediate allergic reaction of Type I (or Type 1) allergy or inflammation related to chronic diseases (IgG1, IgG2, IgG3).

IgG4 in fact is considered as preventative screening as they block access of IgE to the allergen, helping us to understand how your immune system is reacting to food antigens before an allergic reaction is developed.

The concentration of IgG4 is about 10,000 times higher than the IgE concentration. Therefore, IgG4 can bind faster and with greater frequency to the allergen than IgE mapping your immune response to food allergens.

IgG4 antibodies result in only 1% of the histamine released by IgE, with few patients experiencing allergic symptoms. Therefore, IgG4 antibodies are mostly produced when the allergy is asymptomatic.

The primary function of IgG4 is to influence the immune-inflammatory response without the release of histamine factors (the main cause of inflammatory reactions), having the possibility to explore how the amount of IgG4 antibodies could be related to some of your symptoms (bloating, abdominal cramps, headaches to mention some). This will be the first step on your journey to find a better version of yourself.

For food intolerance, the presence of specific IgG antibodies (IgG4) will inhibit the degranulation of mast cells and activation of allergic symptoms (this will not exclude you from experiencing digestive imbalance, headaches, and inflammatory reactions but not as serious as anaphylactic symptoms).

Food items responsible for intolerance can be reintroduced in small quantities while monitoring how much you can eat without causing symptoms after following an elimination diet of six weeks.

Decided IgG4 Testing is the right test for you? Then check out the Intolerance Test here.

References:

1) Tsvetelina Velikova et al. Methods for detection of food Intolerance. Recent Advances in Food Science RAdvFoodScie 2018; 1(3): 106-119

2) Elif Ilgaz Aydinlar, MD; Pinar Yalinay Dikmen, MD; Arzu Tiftikci, MD; Murat Saruc, MD; Muge Aksu; Hulya G. Gunsoy; Nurdan Tozun, MD. IgG-Based Elimination Diet in Migraine Plus Irritable Bowel Syndrome. American Headache Society 2012

3) Hong Sub Lee and Kwang Jae Lee. Alterations of Food-specific Serum IgG4 Titers to Common Food Antigens in Patients with Irritable Bowel Syndrome. J Neurogastroenterology and Motility 2017; 23(4): 578-584

COMBINED ALLERGY & INTOLERANCE TESTING

3) IgG4 & IgE Science

The lab team at Allergy Test are proud to offer a comprehensive range of tests for you to choose from, depending on what you’re looking to get tested.

Our IgG4 and IgE combined testing is the most complete way to ensure you’re getting accurate testing that works for you.

The Allergy & Intolerance Test & Allergy & Intolerance Test Plus offers both immunological and non-immunological responses, giving you a full overview of your body and the more specific reactions caused when you are fighting foreign substances via antigens.

In the last few decades, scientists have been examining the relationship between abnormal nutritional reactions and health issues which has gained a lot of interest. (1, 2) The prevalence of IgE-mediated allergy food reactions appears to be on the rise, and it’s estimated that food intolerance affects about 60% of the population (3).

Abnormal reactions to IgE food antigens can be classified as immune-mediated with the clinical manifestations of anaphylactic reactions. Non-IgE mediated symptoms can include atopic dermatitis, enterocolitis, oesophagitis. (4-5)

IgE antibodies are involved in Type I (or Type 1) allergies and they can cause rapid type immune reactions, with symptoms occurring within few minutes to two hours after eating a specific food, while IgG antibodies are responsible for delayed immune reaction in food known as Type III (or Type 3) allergies with symptoms occurring within few hours to few days.

Both immune-mediated and non-immune-mediated reactions are involved in food intolerance development. The immune mechanism involved in food intolerance is associated with the formation of specific IgG antibodies.

IgG antibodies are involved in the formation and accumulation in various organs of food protein complexes, resulting in inflammatory processes (6-7). In scientific literature, it is reported that 50% of patients affected by chronic diseases may possess IgG delayed mediated food intolerances (aka Type III or Type 3) (8).

IgE and IgG4 Combined Science

Both IgE and IgG antibodies are in closed proximity on chromosome 14 and they are read in sequence. Their production depends on the presence of Interleukins (ILs). In fact, when IL4 is released, it can be assumed that an IgE (Type I or Type 1 allergy) response will occur, with an immediate food reaction (9-10).

The activation of an inflammatory reaction in terms of the IgE mediated response is due to the release of histamine compounds. The compounds come from the mast cells after the binding of an IgE antibody to the mast cell receptor as a response to the antigen attack. Antigen includes all those external agents that can be recognized as foreign and activate an immune response.

In case of sensitization when IL10 is present, mainly the production of IgG4 antibodies will be involved (9), while if other interleukins are synthesized IgG1, IgG2, IgG3 are mainly produced. The production of IgG1, IgG2, IgG3 antibodies when a specific food is consumed activates the formation of immune complexes with deposition in the body wherever the problem is (11).

Unfortunately, there is a lack of scientific studies showing evidence that the deposition of immune complexes on tissues is connected to specific symptoms, which make the test of IgG1, IgG2, IgG3 antibodies not attractive from an Intolerance testing point of view.

On the contrary, it was demonstrated that those antibodies are playing a role in the identification of allergic reactions of non-specific systemic reactions in which inflammatory processes play a major role (12).

Why combining IgG4 and Ige is best?

With the Allergy & Intolerance Test & Allergy & Intolerance Test Plus tests from Allergy Test, you can test for IgE and IgG4 antibodies at the same time.

Testing for IgE and IgG4 antibodies allows testing for, not only the immediate allergic reactions associated with an immune response (IgE) but also those reactions that are not IgE mediated. These can still cause symptoms as bloating, headaches, stomach cramps, diarrhea.

The IgG4 antibodies are known to be the blocking antibodies preventing the release of histamine factors and the activation of an immediate allergic reaction (Type I or Type 1 allergy). IgG4 antibodies can influence an immune response but not activate that directly.

Our Allergy & Intolerance Test Plus can help you to have a better overview of the specific immune response reactions in the presence of specific allergens. In this way we will be able to draw you a map of the reactions that you can take with you, to start your journey to find a better version of yourself.

Our tests are developed for the identification of specific IgE mediated allergies and IgG4 antibodies reactions. Unfortunately, there are also no IgE mediated allergic reactions and our tests are not able to detect those allergies. IgG4 antibodies are only used for the identification of intolerances and not allergies.

References

1) National Academies of Sciences, Engineering, and Medicine. Finding a path to safety in food allergy: Assessment of the global burden, causes, prevention, management, and public policy. Washington, DC: The National Academies Press. 2017.

2) Macchia D, Melioli G, Pravettoni V, Nucera E, Piantanida M, et al. On behalf of the Food Allergy Study Group (ATI) of the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). Guidelines for the use and interpretation of diagnostic methods in adult food allergy. Clin Mol Allergy. 2015; 13: 27.

3) Johansson SG, Hourihane JO, Bousquet J, Bruijnzeel-Koomen C, Dreborg S, et al A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy. 2001; 56: 813-24.

4) Ortolani C, Ispano M, Pastorello E, Bigi A, Ansaloni R, The oral allergy syndrome. Ann Allergy. 1988; 61: 47-52

5) Waserman S, Watson W, Food allergy. Allergy Asthma Clin Immunol 2011; 7 (1): S7.

6) Sampson HA, Anaphylaxis: persistent enigma. Emerg Med Australas. 2006; 18: 101-2

7) EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies). Scientific Opinion on the evaluation of allergenic foods and food ingredients for labelling purposes. EFSA Journal 2014; 277.

8) Wachholz PA, Durham SR, Mechanisms of immunotherapy: IgG revisited. Curr Opin Allergy Clin Immunol. 2004; 4: 313-8.

9) Tsvetelina V, et al., Methods for detection of food Intolerance. Recent Sensitivity Test Plusin Food Science. 2018; 1(3): 106-119

10) Mullin GE, Swift KM, Lipski L, Turnbull LK, Rampertab SD, Testing for Food Reactions: The Good, the Bad, and the Ugly Nutr Clin Pract. 2010; 25: 192

11) Aalberse RC, Stapel SO, Schuurman J, Rispens T, Immunoglobulin G4: an odd antibody. Clin Exp Allergy. 2009; 39(4): 469-77.