Allergix IgG4 and IgE Food Antibodies

Overview:

The IgE Food Antibody Assessment is a blood test that measures IgE antibodies to 19 of the most allergenic foods. The panel also includes a total IgE measurement. The body can react to foods in many different ways. The prevalence of food allergies in Western countries is rising, with up to 10% of the population affected. This trend likely involves a complex interplay between genetic, epigenetic, and environmental risk factors.1 Testing for IgE food antibodies is useful for individuals who suspect that a food is responsible for causing their symptoms. The presence of circulating antibodies may affect each patient differently. According to the American Academy of Allergy, Asthma, and Immunology, "A key message is that a positive allergy test result (skin or blood) indicates only the presence of allergen-specific IgE (called sensitization). It does not necessarily mean clinical allergy (i.e., allergic symptoms with exposure)."2 Therefore, test results should always be viewed in the context of the overall clinical picture.

• Hives or red, itchy skin
• Stuffy or itchy nose, sneezing or itchy, teary eyes
• Vomiting, stomach cramps or diarrhea
• Angioedema or swelling
• Shortness of breath or wheezing
• Anaphylaxis

Certain allergy risk factors cannot be modified including male sex in children, race/ethnicity (increased among Asian and black children compared with white children), and genetics (familial associations, HLA, and specific genes). However, the following risk factors can be addressed to reduce/prevent food allergy:1

• Increased hygiene
• Microbiome imbalance
• Atopic disease manifestations (comorbid atopic dermatitis)
• Vitamin D insufficiency
• Dietary fat (reduced consumption of omega-3-polyunsaturated fatty acids)
• Reduced consumption of antioxidants
• Increased antacid use (reducing digestion of allergens)
• Obesity (being in an inflammatory state)

Timing and route of exposure to foods. An IgE allergic response involves immediate-hypersensitivity to a substance. It is generally easier for patients and clinicians to identify a food that causes an immediate response, although not always, and testing serum IgE antibodies can be helpful.

The National Institute of Allergy and Infectious Disease (NIAID) guidelines state that a combination of medical history, physical examination, and oral food challenge can assist in the diagnosis of food allergy, with the oral food challenge being the gold standard.3 In some instances, an oral food challenge may be dangerous for the patient and other tools may be helpful.
A skin-prick test involves the injection of an allergen on the skin then observation for a reaction. This method has low specificity and low positive predictive value,3 and the injection of a substance that can potentially cause a serious reaction should be monitored closely. Serum testing can be especially useful when skin-prick tests cannot be performed (for example, due to extensive dermatitis or dermatographism), or when antihistamines cannot be discontinued.
Allergen-specific serum IgE testing does not involve introducing an allergen in order to test. Instead, already circulating antibodies are measured, however, the patient must have been exposed to the allergen in the days leading up to testing in order to detect antibodies. The NIAID suggests, "sIgE tests are useful for identifying foods potentially provoking IgE-mediated food-induced allergic reactions and specified "cutoff" levels, defined as 95% predictive values, may be more predictive than skin prick tests of clinical reactivity in certain populations, but when used alone they are not diagnostic of food allergy."3

Sicherer S and Sampson H. Food allergy: A review and update on epidemiology, pathogenesis, diagnosis, prevention, and management. J All Clin Immunol. 2018;141(1):41-58.

Cox L, Williams B, Sicherer S, et al. Pearls and pitfalls of allergy diagnostic testing: Report from the American college of allergy, asthma and immunology/American academy of allergy, asthma and immunology specific IgE test task force. Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology. 2009;101(6):580â??92.

NIAID- Sponsored Expert Panel. Guidelines for the Diagnosis and Management of Food Allergy in the United States: Report of the NIAID-Sponsored Expert Panel. J All Clin Immunol. 2010;126(6 suppl):S1-58.

Circulating IgG4 food antibodies are not diagnostic for a specific condition but indicate an immune response to the presence of food antigens. IgG4 antibodies are produced in a delayed hypersensitivity reaction, which can occur one to seven days after exposure to the offending food antigen. These reactions are difficult to detect since there may be no obvious association with the offending food. Commonly reported symptoms for elevated IgG4 responses involve GI tract, skin, nose, and throat. In contrast, the immune response could be a normal response that would not necessarily cause symptoms. Therefore, test results should always be viewed in the context of the overall clinical picture.

Conditions associated with IgG4 food antibodies:

• Eosinophilic esophagitis
• Irritable bowel syndrome/ GI symptoms
• Crohn's disease

Of the 5 classes of antibodies, immunoglobulin G (IgG) is the most abundant circulating antibody, making up 75% of antibodies. The other classes of antibodies include IgE, IgA, IgM, and IgD. IgG has 4 subclasses including IgG1, IgG2, IgG3, and IgG4 making up 66%, 23%, 7%, and 4% of the IgG antigen pool respectively.

IgG4 is unique compared to the other subclasses. It acts as a blocking antibody to the allergy-producing IgE antibody, and with the IgE antibody, is considered part of the Th2 response. Increases in IgG4 levels correlate with improved clinical responses since it blocks the IgE anitbody allergic response; it is involved in establishing immunologic tolerance to that food. IgG4 does not activate complement compared to IgE3. Some speculate that IgG4 may be produced initially to attenuate IgE-mediated disease, but ultimately results in a pro-inflammatory process in susceptible atopic hosts. IgG food antibodies can result in a delayed symptom response to a food.1 Whereas IgE antibodies can result in immediate-hypersensitivity to a substance. It is generally easier for patients and clinicians to identify a food that causes an immediate response. A delayed-response to food may be more challenging to determine, and testing can be helpful. The IgG Food Antibody Assessment evaluates total IgG (1-4) versus only testing for IgG4 and offers a more complete assessment. Clinicians may consider measuring IgG4 in patients with eosinophilic esophagitis.
IgG4 is an allergy blocking antibody, however, scientific societies do not recommend its use in the diagnosis of food allergy. IgG4 testing cannot be substituted for IgE blood testing or skin prick testing for allergy diagnosis.

Other types of adverse food reactions that are not mediated by the immune system are referred to as food intolerances. Food intolerances include lactose intolerance due to lactase enzyme deficiency in the gut; testing is available for suspected lactose intolerance. Testing is not available for all food intolerances. These include vasoactive amines like histamine and tyramine, food additives and preservatives (nitrites, sulfites, MSG, aspartame), salicylates, nightshades, lectins, FODMAPs, oxalates, etc. Since testing is not available for every type of adverse food reaction, the elimination/rechallenge diet remains the gold standard for identification of symptom-producing foods.