Food Sensitivities

Each of our bodies is a unique machine, reacting to different foods in different ways.  Adverse food reactions may occur under a variety of circumstances; some are immediate and may require medical attention, while others are more delayed.  In the latter case, elimination of the culinary culprit from the diet often leads to resolution, but it can be difficult to identify exactly which food(s) are causing the issue.  That is why the IgG Food Antibody test is so important; it relates the necessary information on which foods to avoid to reduce the inflammation seen in disease states such as Irritable Bowel Syndrome (IBS), Major Depressive Disorder, Migraine headaches, skin rashes, joint aches, and Autoimmune disease.  The immune system is highly complex, but it is important to know some of the key differences between IgE and IgG-mediated reactions.

Definition

Immunoglobulins, or antibodies, represent a diverse array of biomolecules that facilitate, through the binding of specific regions of an antigen, the subsequent removal of the stimulus from our body via a complex immune response.  While there are five classes of immunoglobulin (A,D,E,G,M), we will be focusing on two hypersensitivity reactions that are involved in relation to food: IgG and IgE.  Hypersensitivity reactions occur when the normally protective immune system comes into contact with a stimulus and it responds in a way that may potentially harm the body.  A symptomatic reaction only occurs in sensitized individuals, i.e., they must have had at least one prior asymptomatic contact with the offending antigen.  IgG is the most abundant immunoglobulin and is comprised of four subclasses; possessing high affinity and specificity towards antigens, these classes differ in the types of antigen they bind to.  Antigens in our food can trigger the production of IgG antibodies that are part of the adaptive immune system, produced to protect us against foreign invaders.  The production of IgG in response to the introduction of an antigen is a delayed reaction that may occur 3 hours to 3 days after ingestion.  IgE is an immunoglobulin antibody that, when activated, binds to certain immune cells called mast cells, triggering the release of histamine.  Irritable Bowel Syndrome (IBS) is a type of Functional gastrointestinal disorder (FGID), defined as disorders of the digestive system in which symptoms cannot be explained by the presence of structural or tissue abnormality (1). There is no cure for IBS, and management focuses on symptom relief (2).

Etiology

Food allergy is an abnormal immune response to an ingested food, and is considered a Type I Hypersensitivity reaction when immediate allergic reactions (e.g., food, pollen, allergies, asthma, anaphylaxis) occur.  When an allergen is first exposed to a susceptible individual, it activates TH-2 lymphocytes that secrete cytokines, to drive production of allergen-specific IgE immunoglobulin from B cells.  These IgE molecules bind to IgE receptors on mast cells and basophils in a process known as sensitization.  When re-exposed to the same antigen, the IgE bound on mast cells and basophils becomes cross-linked, resulting in the release of inflammatory and vasoactive mediators, such as histamine (5), resulting in the immediate onset of symptoms associated with a Type I hypersensitivity reaction.  Type 1 food allergy reactions can occur in seconds and up to 30 minutes after exposure; it may affect multiple organs, and in some cases, be severe or even life threatening.  Type III hypersensitivity reactions is another type of abnormal immune response that involves immunoglobulins, but is more delayed than Type I, generally occurring from 3 -36 hours after consumption of the offending agent.  An IgG Type III hypersensitivity reaction begins in the gastrointestinal tract where “leaky gut”, or compromised GI integrity, has occurred, via inflammation caused by poor digestion, unbalanced gut microflora, excess alcohol intake, or using certain medications.  “Leaky gut” increases the probability that larger food particles can enter the bloodstream and this creates the potential for those food particles to trigger a delayed, food-specific IgG immune response (3).  IgG molecules bind with the food antigens, forming antigen-antibody immune complexes that are deposited in tissues.  Inflammation, emerging as a consequence of this process, is chronically sustained by repeated consumption of allergenic foods (6).

Clinical Presentation

Patients who suffer from adverse food reactions manifest a spectrum of symptoms ranging from transient and benign symptoms such as dysphagia, vomiting, bloating, hives, and loose stools to potentially life-threatening reactions such as anaphylaxis (5).  The IgE-mediated reaction is an immediate and potentially life-threatening situation presenting with abdominal pain, urticaria, pruritus, hypotension, syncope, wheezing, swelling, and anaphylaxis.  IgG-mediated reactions have a delayed onset and can lead to chronic inflammation and intolerance.  This type of reaction may present in a variety of symptoms, such as anemia, weight loss, malabsorption, failure to thrive, chest pain, or refractory heartburn.   

Testing

It is important that we don’t confuse Food Allergy Testing with Food Sensitivity Panel; the former is an analysis of IgE while the latter deals with IgG.  Food Allergy Testing is typically a skin test where a food antigen is deposited in the cutaneous matrix and the subsequent Type I hypersensitivity reaction generally occurs within 30 minutes, indicated by a red, swollen mark on the skin (wheal).  A Food Sensitivity Panel measures the presence of IgG, produced from repeated exposure to certain antigens in food that would normally contribute to a Type III, delayed, hypersensitivity reaction.  If a long time has passed since ingesting the food, an IgG reaction may not occur due to a decline in the production of that particular IgG; this test is more sensitive for IgG to foods that have been recently consumed.  Due to a lack of consumption, a negative IgG reaction may be reported, even if there was an IgE allergy present from a skin test.  Some antigen regions are very similar to others, making it possible to react to an antigen even if you haven’t eaten that food before.  This false positive occurs as a result of cross-reactivity, a phenomenon that occurs when foods (or pollen) contain similar antigens.  For example, if we test someone that has a birch pollen allergy, the IgG test may show an immune response to peanuts, hazelnuts, raw apples and/or peaches due to cross-reactivity.  

Remediation

Traditionally, the gold standard for food allergy diagnosis has been to eliminate the suspected food from the diet then challenge the body with it again to confirm via reaction.  The first step is elimination of the food trigger through proper identification and avoidance.  Secondly, it is important to be able to recognize the signs of a Type 1 versus a Type III hypersensitivity reaction so that epinephrine administration isn’t delayed.  Those that have IgE-mediated allergies should carry intramuscular epinephrine with them in the case of accidental exposure; those with non-IgE-mediated allergies do not require self-injectable epinephrine.  Finally, education about food-trigger avoidance, cross-contamination and cross-reactivity should be emphasized (5).  Dietary interventions to help relieve symptoms, including the elimination approach, do not recognize that food triggers a) are unlikely to be limited to just these foods and b) are subject to interpatient variability (3).  Therefore, a successful targeted approach suggests a personalized regimen, where each dietary intervention is personalized and based on specific food-IgG results. 

Note: 

IgG food sensitivities testing is not recommended for individuals using corticosteroids or immune-suppressing drugs due to reduced production of IgG antibodies that may decrease reactivity on a food sensitivity panel.

References:

romecriteria.org/criteria

Mansueto P. et al (2015) Food allergy in irritable bowel syndrome: The case of non-celiac wheat sensitivity. World J Gastroenterol.21:7089–109.

Hart, Gillian. Food-Specific IgG Guided Elimination Diet; Role in Irritable Bowel Syndrome? Int J Nutr Sci & Food Tech 3:4, 47-49, 2017.

Sampson HA. Differential diagnosis in adverse reactions to foods. J Allergy Clin Immunol. 1986;78(1):212–9.

Leung, J., Dadlani, A., Crowe, S.E. Essential Medical Disorders of the Stomach and Small Intestine, Chapter 21: Food Allergies, Food Intolerances, and Carbohydrate Malabsorption.  Springer Nature, 2019.

Karakula-Juchnowicz, H., et al. The role of IgG hypersensitivity in the pathogenesis and therapy of depressive disorders. Nutritional Neuroscience, 2014.

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