Gamma-Gliadin IgG

Gamma-gliadin is a sulfur-rich protein found in wheat gluten, contributing to the structure and elasticity of dough; it also plays a key role in immune reactions related to celiac disease and wheat allergy. 

Clinically, gamma-gliadin is recognized as a major antigen targeted by antibodies in celiac disease and as a frequent allergen in wheat-induced food allergies.

What is Gamma-Gliadin?

Gamma-gliadin is a component of gluten.

Gluten Composition

Gluten is a protein complex found in wheat, barley, and rye. It is primarily composed of smaller proteins called gliadins and glutenins. Gliadins are further classified into alpha, beta, gamma, and omega subtypes, each contributing differently to gluten structure and human health impacts.

Understanding Gamma-Gliadins

Gamma-gliadins are sulfur-rich (S-rich) members of the gliadin family. They help stabilize the gluten network through disulfide bond formation, contributing to wheat dough's elasticity and viscosity. 

Gamma-gliadins are present in moderate amounts—more abundant than omega-gliadins but less than alpha/beta-gliadins. Environmental factors, nitrogen fertilization, and wheat cultivar genetics all influence their production.

Gamma-Gliadin in Celiac Disease

Gamma-gliadins are immunologically important in celiac disease (CD). They contain T-cell stimulatory and B-cell epitopes recognized by patients with CD, including:

• The QPEQPFP epitope, a dominant target of anti-gliadin antibodies.
• Epitopes that stimulate T-cells when deamidated by tissue transglutaminase (TG2) and presented by HLA-DQ2 or HLA-DQ8.

Gamma-gliadin-specific antibodies often appear earlier and dominate over alpha-gliadin antibodies in CD. These antibodies are relevant to serologic testing (e.g., deamidated gliadin peptide (DGP) IgG assays) and can cross-react with alpha-gliadin peptides.

Gamma-Gliadin in Wheat Allergy

Gamma-gliadins are also clinically significant in wheat-related food allergies. Around 62% of wheat-allergic individuals have IgE antibodies against gamma-gliadins, making them major allergens. They:

• Elicit strong IgE-mediated reactions via gastrointestinal sensitization.
• Contain dominant IgE-binding epitopes, especially in their N-terminal regions.
• Trigger basophil degranulation and other allergic immune responses.

Gamma-gliadins are involved in both classical wheat food allergy and wheat-dependent exercise-induced anaphylaxis.

Clinical Relevance as a Biomarker

Testing for an immune response against gamma-gliadins may be beneficial in the following scenarios:

In Celiac Disease

Gamma-gliadin IgG is a target in anti-DGP antibody assays and may help detect immune activity, especially in early or atypical CD cases.

In Wheat Allergy

Gamma-gliadins are a major IgE-binding component; additional testing such as gamma-gliadin IgG should be considered when assessing broader wheat-specific responses.

What is Gamma-Gliadin IgG?

The immune system produces IgG (Immunoglobulin G) antibodies to target specific proteins, known as antigens. The body may produce IgG antibodies against gluten proteins, including gliadin, in gluten-related disorders.

Gamma-Gliadin IgG in Gluten-Related Disorders

In celiac disease, gamma-gliadin is a major antigen targeted by the immune system. 

Gamma-gliadin IgG antibodies are among the first gluten-related antibodies to appear, often before other antibodies. These antibodies frequently cross-react with related alpha-gliadin peptides, but gamma-gliadin remains their primary target.

Although deamidation (a modification by tissue transglutaminase, tTG) increases immune recognition of some gliadin peptides, gamma-gliadin IgG antibodies bind both deamidated and native gamma-gliadin similarly.

When is Gamma-Gliadin IgG Testing Relevant?

Gamma-gliadin IgG testing may be relevant in the following scenarios:

Celiac Disease Diagnosis

Gamma-gliadin IgG may be measured as part of the antibody panel for suspected CeD. However, IgA-based tests (tTG-IgA and EMA-IgA) remain the first-line tests in IgA-sufficient individuals.

Non-Celiac Gluten Sensitivity (NCGS)

Gamma-gliadin IgG may sometimes be elevated, but its role in diagnosing NCGS is unclear. NCGS is generally a diagnosis of exclusion.

In both celiac disease and NCGS, gamma-gliadin IgG may offer early clues about an immune reaction.

IgA Deficiency

In patients with selective IgA deficiency, gamma-gliadin IgG testing and other IgG-based assays become more important for evaluating celiac disease.

Dietary Monitoring

Gamma-gliadin IgG levels may decrease on a gluten-free diet, but they are less reliable than tTG-IgA for monitoring dietary adherence.

Food Allergies vs. Food Sensitivities

Food allergies and food sensitivities are different immune responses to food. Whether a person has a food allergy or food sensitivity, the proteins in a particular food are often (but not always) responsible for triggering the immune system's reaction. 

Food allergies, typically IgE-mediated, cause immediate, sometimes severe reactions like anaphylaxis within minutes to hours of eating the food, often triggered by common allergens like nuts, seafood, or dairy. 

On the other hand, food sensitivities are more common and involve delayed non-IgE-mediated immune reactions, such as gastrointestinal discomfort or skin issues, and they usually occur hours or days after consuming the food. They may involve an IgG-mediated immune response, and other immune-mediated chemicals may also be present.

While food allergies can cause life-threatening reactions like anaphylaxis and are often identified early, food sensitivities are not life-threatening and can be managed with dietary changes. 

Both are triggered when the immune system mistakenly identifies food proteins as harmful. However, food allergies involve an immediate IgE response, while food sensitivities are due to a delayed immune reaction.

What is Food Sensitivity Testing?

Food sensitivity testing such as this panel identifies various immune reactions, helping clinicians pinpoint which foods may trigger symptoms. 

This testing can be helpful when it’s important to differentiate food sensitivities from food allergies, as they require different management strategies. Unlike traditional allergy testing, which focuses on immediate responses, food sensitivity testing can reveal delayed, less obvious reactions.

What is Tested for in Food Sensitivity Testing?

Different companies offer different panels, which may assess various biomarkers. Increasingly, a combination of the following biomarkers are seen: 

Antibodies

IgG, IgA, IgM, and IgE antibodies are primary biomarkers for food sensitivities. IgG is a commonly tested antibody in food sensitivity panels, as it reflects a delayed, chronic immune response. 

IgA and IgM are also assessed regarding mucosal immunity and initial immune responses, respectively. 

IgE is typically tested in food allergy testing, but it can sometimes be part of food sensitivity panels if a clinician suspects combined allergic reactions and sensitivities.

Testing Procedure

Gamma-gliadin IgG testing may be done with serum or blood spot samples. 

Venipuncture-Based Testing

This is the most widely used approach in clinical laboratories. A healthcare professional collects a blood sample via standard venipuncture, usually from a vein in the arm. 

The sample is processed to separate the serum, which is then analyzed using enzyme-linked immunosorbent assay (ELISA) or related immunoassay techniques. The assay detects and quantifies gamma-gliadin-specific IgG antibodies present in the serum.

Blood Spot Testing

For remote or home-based testing, dried blood spot (DBS) collection is an alternative. 

A small finger-prick is used to collect capillary blood onto specialized filter paper. Once dried, the blood spot is sent to a laboratory, where gamma-gliadin IgG antibodies are eluted and measured, usually via adapted ELISA protocols. 

While convenient, DBS testing may have slightly lower sensitivity compared to serum-based assays due to lower sample volume and matrix effects.

In both methods, the test result reflects the presence and concentration of IgG antibodies directed against gamma-gliadin peptides, which may be used in conjunction with other clinical data when assessing gluten-related disorders.

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