Understanding wheat reactions: clarifying the confusion around gluten and beyond

This article seeks to address the high number of queries we receive regarding the variety of possible responses to wheat and gluten. 

At CNSLab we specifically cover IgG immune-mediated sensitivity reactions to wheat and gliadin/gluten.

Our test does not cover type 1 IgE allergy to wheat, coeliac disease or non-coeliac gluten sensitivity (NCGS). If the word allergy means ‘immune confusion’, then we seek to clarify the terminology.

Reactions to wheat

Reactions to wheat can be categorised into immunological, non-immunological, and autoimmune responses. These reactions vary in their underlying mechanisms, symptoms, and diagnostic approaches.

Here is an overview of the main types of wheat-related reactions and the tests associated with each.

1. Coeliac disease (autoimmune reaction)

Mechanism

An autoimmune condition triggered by gluten (a protein found in wheat, barley, and rye) in genetically predisposed individuals (HLA-DQ2/DQ8 haplotypes). Gluten ingestion leads to intestinal inflammation and villous atrophy.

Symptoms

Chronic diarrhoea, abdominal pain, bloating, malabsorption, weight loss, fatigue, anaemia, and extra-intestinal manifestations like dermatitis herpetiformis and neurological conditions.

Testing

Serological tests

• Anti-tissue transglutaminase (tTG) IgA antibodies (primary screening test).
• Anti-deamidated gliadin peptide (DGP) IgG antibodies (useful for IgA-deficient individuals).
• Total IgA to exclude IgA deficiency (common in coeliac patients).

Genetic testing

HLA-DQ2/DQ8 typing (to exclude coeliac disease in ambiguous cases).

Confirmatory test

Small intestinal biopsy showing villous atrophy and crypt hyperplasia while consuming gluten, although recent guidelines have suggested that the laboratory testing listed above is sufficient in non-complicated cases. 

2. Wheat allergy (IgE-mediated hypersensitivity)

Mechanism

An IgE-mediated allergic reaction to wheat proteins (not just gluten), leading to rapid hypersensitivity responses.

Symptoms

Urticaria, angioedema, respiratory symptoms, gastrointestinal distress, and in severe cases, anaphylaxis. Symptoms often occur within minutes to hours after exposure.

Testing

Skin Prick Test (SPT)

Measures immediate allergic response to wheat extracts.

Serum specific IgE testing

Measures wheat-specific IgE levels (using platforms like ImmunoCAP or similar).

Oral Food Challenge (OFC)

Gold standard for confirming clinical allergy under medical supervision. An OFC is when a client is fed a certain food under close medical supervision, as there is some risk of their being allergic. It starts with a small amount of the food which is gradually increased (usually every 20 minutes), until a reaction occurs, or the ‘top dose’ is eaten without any allergic reaction. This dose/amount is registered as it is the level at which a food can be tolerated without symptoms. A food challenge usually lasts between 3 to 6 hours, most commonly around 5 hours.

Component-Resolved Diagnostics (CRD)

Identifies specific allergenic wheat proteins (e.g., ω-5 gliadin, associated with exercise-induced anaphylaxis), which are becoming more popular in order to precisely identify the target allergen or component of the allergen.

3. Non-Celiac Gluten Sensitivity (NCGS)

Mechanism

A non-autoimmune, non-IgE-mediated response to gluten or other wheat components, such as amylase-trypsin inhibitors or fructans. Data obtained from survey studies suggest that the prevalence rates of NCGS range from 0.49% to 14.9%, which are higher than almost all the prevalence rates estimations of coeliac disease or wheat allergy.

Symptoms

Symptoms overlap with coeliac disease and irritable bowel syndrome (IBS), including bloating, abdominal pain, diarrhoea, fatigue, and brain fog. However, unlike coeliac disease, NCGS does not cause intestinal damage.

Testing

Exclusion of coeliac disease and wheat allergy

Essential for diagnosing NCGS, as there are no definitive biomarkers for this condition.

IgG food sensitivity testing

While not diagnostic of NCGS, IgG testing can help identify specific IgG responses to wheat or gluten, which may provide additional insights into potential triggers contributing to symptoms.

Symptom monitoring with elimination and challenge diets

Clinical improvement on a gluten-free diet, followed by recurrence of symptoms upon gluten reintroduction, remains a key approach to identifying NCGS.

4. Irritable Bowel Syndrome (IBS) and wheat intolerance

Mechanism

 A complex condition with many possible causes, one such cause is a non-immunological intolerance to fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) in wheat (e.g., fructans).

Symptoms

 Gas, bloating, diarrhoea, constipation, and abdominal discomfort.

Testing

Hydrogen and methane breath testing

Evaluates malabsorption of FODMAPs like fructose.

Symptom monitoring

FODMAP elimination and reintroduction.

5. IgG-mediated wheat sensitivity

Mechanism

Delayed hypersensitivity reaction involving IgG antibodies against wheat proteins, leading to the formation of immune complexes, initiating low grade inflammation.

Symptoms

Non-specific symptoms such as bloating, fatigue, headaches, or joint pain, often reported hours to days after wheat consumption.

Testing

Food-specific IgG testing

This test measures IgG antibodies to wheat and gluten proteins (e.g., gliadin) using ELISA or multiplex platforms such as FoodPrint. Wheat contains numerous antigenic targets beyond gluten that can elicit specific IgG responses. Antigens are markers that your immune system recognises, such as a protein or a string of amino acids. Testing for gluten alone may overlook sensitivity reactions to other components of whole wheat.

Gluten is one of the major antigenic components of wheat and is particularly relevant as it is the primary target in coeliac disease. Testing for gluten individually can provide valuable insights, particularly when combined with whole wheat testing. A positive result for anti-gluten IgG antibodies may suggest the need for dietary exclusion of other gluten-containing grains, such as barley and rye.
However, it is important to note that the detection of anti-gluten IgG antibodies in this context is not diagnostic of coeliac disease. Coeliac diagnosis requires specific clinical tests, as outlined above, and this assay is not calibrated for such a purpose. The presence of IgG antibodies may indicate an association but should be interpreted within the broader clinical context.

Clinical interpretation

Best used as part of a comprehensive evaluation, considering symptom diaries and elimination diets.

Diagnostic approach summary

Initial screening

Based on clinical presentation, family history, and symptom timing.

Targeted testing

Dietary trials

Use elimination diets (e.g., gluten-free or low-FODMAP) with symptom monitoring.

By identifying the specific wheat-related reaction, tailored management strategies can be implemented to improve patient outcomes.

CNSLab FoodPrint and FoodDetective IgG testing and frequently asked questions

On our various food panels we test for IgG immune-mediated reactions to the gluten-containing grains wheat, barley, rye, durum wheat, couscous and spelt. We test durum wheat separately as it is a different species of wheat, Triticum Durum, from common wheat or bread wheat, Triticum Aestivum, therefore its protein structure is marginally different and may potentially stimulate a different immune response. The same may be true for spelt, species Triticum Spelta. Couscous derives from durum wheat and not bread wheat, and during its processing its protein structure may also change which explains our rationale for testing separately. 

We test for gliadin separately. Gliadin is the most abundant protein in gluten. We test for gliadin separately because we make our food product extracts from the whole food source, testing the complete combination of food proteins together. However, during processing, gliadin is leeched from the solution due to its non-soluble properties and is not present in the final product.  

Therefore, on our report the following advice should be followed:

We offer free test interpretations for all our tests, and free training. Please contact the nutrition department at nu*******@*****dx.com to book an appointment or receive a link to our monthly training interactive webinars.