IgE and IgG food intolerance testing: Are they reliable?

Food intolerance, sometimes used interchangeably with food “allergy,” is a challenging and sometimes life-threatening condition in which sufferers mount an immune response against certain foods. Some reactions to food are not subtle. For example, a child with a severe allergy to peanuts may develop a life-threatening reaction called anaphylaxis, which can interfere with breathing, cause blood pressure to drop to dangerously low levels, cause fluid accumulation in the lungs, and abnormal heart rhythms. On the other hand, patients with mild lactose intolerance may experience only mild bloating and loose stools whenever they consume cow’s milk.

All too often, people who are ultimately diagnosed with food intolerance receive the diagnosis only after seeing several physicians and specialists because of non-specific gastrointestinal complaints. This can be deeply troubling for patients and their families, so prompt diagnosis is an important part of food allergy management.  

Is it food intolerance or allergy?

The human body can react differently to different foods and some people may react severely to a food while others do not react at all. In some cases, a person lacks the ability to digest or metabolise a certain molecule contained in the particular food.

For example, people with true lactose intolerance cannot digest the sugar, lactose, because they do not make enough of an enzyme (lactase) that breaks down lactose. This means that excess lactose is present in the gastrointestinal tract, which causes diarrhoea.

Conversely, children some exhibit a condition called cow’s milk allergy during the first 1-2 years of life. 

People with cow's milk allergy experience a true allergic reaction to proteins within milk (e.g. alpha-s1-casein) in which the immune system reacts to actual substances within the milk. Despite the different mechanisms, cow's milk allergy causes bloating and diarrhoea, similar to lactose intolerance.

Thus, the difference between food intolerance and food allergy is that intolerance results from an inability to process compounds within foods while allergy indicates that the immune system reacts to an allergen or allergens within food. However, the clinical symptoms of the two conditions may be quite similar.

Skin testing for food allergy

Since a food allergy is due to an allergic reaction to allergens within food, it is at least theoretically possible to test for cells within the immune system that react to specific food allergens.

For example, people can undergo skin hypersensitivity testing (i.e. allergy testing) in which a small bit of allergen is placed under the skin and the skin is observed for a weal and flare reaction. This reaction is characteristic of an allergy and is caused by a specific type of antibody called an IgE antibody.

Skin allergy testing can be useful for many types of allergies because the results are rapidly obtained, the test is fairly sensitive, and it is relatively inexpensive.

IgE antibody testing

Tests for the presence of IgE antibodies that specifically react to certain allergens are also available. IgE tests are more expensive and less sensitive than skin testing. They are widely available and are unaffected by the presence of other drugs in the patient's system. Skin testing may fail to show reaction in a person who is taking antihistamines, for example, while IgE testing would not. IgE tests are also helpful in people who have potentially severe allergies and may experience anaphylaxis simply from having a small bit of antigen placed under the skin.

Unfortunately, people can have significant food allergies based on clinical symptoms and signs, but may exhibit high, medium, low, or even negative results in IgE antibody testing. While high levels of IgE antibodies against the food allergen typically indicate a severe allergy, this is not always the case. Moreover, some people without any detectable IgE antibodies may have significant allergies to certain foods.

IgG antibody testing

IgG, like IgE, is a type of antibody. The presence of IgG can be used to determine if someone has been exposed to certain viruses such as hepatitis B and varicella, the virus that causes chickenpox.

Food specific IgG and IgG4 tests are available, but their role in food intolerance testing is questionable. The presence of food-specific IgG4 antibodies does not correspond to an actual allergic reaction to food. In fact, there is some evidence that the presence of IgG4 antibodies may suggest that people are either tolerant of the food or that they do not have an allergy to it at all.

The IgG4 antibody appears to indicate that the body is exerting anti-inflammatory responses to a food, while in reality, mechanisms of increased tolerance are at work. In other words, the presence of food-specific IgG4 antibodies may simply reflect the person’s typical response to a certain food.

IgG and IgE antibodies appear to respond in opposite ways in relation to certain food allergies. For example, cow’s milk allergy is common in young children, but most outgrow it by the age of three. As children outgrow the allergy, levels of IgE antibodies decrease while those of IgG4 antibodies increase. The same effect can be seen in children who are allergic to chicken eggs and peanuts; as children receive treatment for these allergies, IgE levels decrease and IgG4 levels increase.

So, what does this all mean?

Skin hypersensitivity testing is the most useful in the diagnosis of food allergy.

While IgE antibody testing may be useful in the diagnosis of some food allergies, it is more expensive, takes longer, and is less sensitive than skin hypersensitivity testing. Additionally, people can have severe food allergies but show negative results on IgE antibody testing.

IgG antibody testing is an unreliable test for the diagnosis of food allergy. In fact, the presence of IgG antibodies may actually reflect tolerance or lack of allergy to a particular food rather than the presence of disease. Therefore, food specific IgG4 tests should not be used to diagnose food allergies. Furthermore, foods should not be eliminated from the diet based on the results of IgG4 antibody testing.

References

1. Wasserman RL, Factor JM, Baker JW, et al. Oral immunotherapy for peanut allergy: multipractice experience with epinephrine-treated reactions. J Allergy Clin Immunol Pract. Jan-Feb 2014;2(1):91-96. doi:10.1016/j.jaip.2013.10.001
2. Heaney RP. Dairy intake, dietary adequacy, and lactose intolerance. Adv Nutr. Mar 2013;4(2):151-156. doi:10.3945/an.112.003368
3. Scrimshaw NS, Murray EB. The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance. Am J Clin Nutr. Oct 1988;48(4 Suppl):1079-1159.
4. Caspary WF. Diarrhoea associated with carbohydrate malabsorption. Clin Gastroenterol. Jul 1986;15(3):631-655.
5. Host A. Frequency of cow's milk allergy in childhood. Ann Allergy Asthma Immunol. Dec 2002;89(6 Suppl 1):33-37.
6. Chatchatee P, Jarvinen KM, Bardina L, Beyer K, Sampson HA. Identification of IgE- and IgG-binding epitopes on alpha(s1)-casein: differences in patients with persistent and transient cow's milk allergy. J Allergy Clin Immunol. Feb 2001;107(2):379-383. doi:10.1067/mai.2001.112372
7. Ahmed AR, Blose DA. Delayed-type hypersensitivity skin testing. A review. Arch Dermatol. Nov 1983;119(11):934-945.
8. Hamilton RG, Franklin Adkinson N, Jr. In vitro assays for the diagnosis of IgE-mediated disorders. J Allergy Clin Immunol. Aug 2004;114(2):213-225; quiz 226.
9. Sampson HA. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol. May 2001;107(5):891-896. doi:10.1067/mai.2001.114708
10. Maruyama T, Schodel F, Iino S, et al. Distinguishing between acute and symptomatic chronic hepatitis B virus infection. Gastroenterology. Apr 1994;106(4):1006-1015.
11. Jenke AC, Klein S, Baiker A, et al. Serologic analysis of the IgG antibody response in children with varicella zoster virus wild-type infection and vaccination. Pediatr Infect Dis J. Nov 2012;31(11):1148-1152. doi:10.1097/INF.0b013e31826bac27
12. Beyer K, Teuber SS. Food allergy diagnostics: scientific and unproven procedures. Curr Opin Allergy Clin Immunol. Jun 2005;5(3):261-266.
13. Boyce JA, Assa'ad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol. Dec 2010;126(6 Suppl):S1-58. doi:10.1016/j.jaci.2010.10.007
14. Aalberse RC, Stapel SO, Schuurman J, Rispens T. Immunoglobulin G4: an odd antibody. Clin Exp Allergy. Apr 2009;39(4):469-477. doi:10.1111/j.1365-2222.2009.03207.x
15. Savilahti EM, Rantanen V, Lin JS, et al. Early recovery from cow's milk allergy is associated with decreasing IgE and increasing IgG4 binding to cow's milk epitopes. J Allergy Clin Immunol. Jun 2010;125(6):1315-1321 e1319. doi:10.1016/j.jaci.2010.03.025
16. Caubet JC, Bencharitiwong R, Moshier E, Godbold JH, Sampson HA, Nowak-Wegrzyn A. Significance of ovomucoid- and ovalbumin-specific IgE/IgG(4) ratios in egg allergy. J Allergy Clin Immunol. Mar 2012;129(3):739-747. doi:10.1016/j.jaci.2011.11.053
17. Jones SM, Pons L, Roberts JL, et al. Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol. Aug 2009;124(2):292-300, 300 e291-297. doi:10.1016/j.jaci.2009.05.022
18. Stapel SO, Asero R, Ballmer-Weber BK, et al. Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report. Allergy. Jul 2008;63(7):793-796. doi:10.1111/j.1398-9995.2008.01705.x