Alpha-Gliadin IgA

Alpha-gliadin, a component of gluten proteins found in wheat and related grains, is important in the pathogenesis of celiac disease due to its high proline and glutamine content.

These residues make alpha-gliadin particularly immunogenic, leading to various immune responses in genetically susceptible individuals. 

In celiac disease, the immune system produces antibodies including IgA and IgG antibodies against alpha-gliadin peptides, triggering both innate and adaptive immune responses.  These include T cell recognition via HLA-DQ2 or HLA-DQ8 molecules and antibody production. 

While alpha-gliadin IgA antibodies are a marker for gluten sensitivity and celiac disease, they can also be present in non-celiac gluten sensitivity and other conditions, making them useful but not definitive for diagnosis. 

The presence of these antibodies often necessitates further testing, including anti-tissue transglutaminase and endomysial antibodies, to confirm celiac disease.

What is Alpha-Gliadin?

Alpha-gliadin is one subtype of gliadin.  Other subtypes include beta-gliadin, gamma-gliadin and omega-gliadin.  [12.] 

Alpha-gliadin is a component of gluten proteins found in wheat and related grains. It contains several peptide sequences that are particularly toxic to individuals with celiac disease, known as gliadin toxic peptides.

Alpha-gliadin is considered to be important in the context of celiac disease due to its high content of proline (P) and glutamine (G) residues, which are important in celiac disease pathogenesis.  [9.] 

Immune Response Against Alpha Gliadins  [2., 13.]

The immune response to alpha-gliadins is a complex process that plays a central role in celiac disease pathogenesis.  It includes multiple responses by the immune system to various protein and peptide components in sensitive individuals.  

Specific components of the immune response include: 

T Cell Recognition

Alpha-gliadins contain multiple immunogenic peptides that are recognized by T cells in celiac disease patients. 

These peptides bind to HLA-DQ2 or HLA-DQ8 molecules on antigen-presenting cells, triggering a T cell response. 

The most immunogenic alpha-gliadin peptides include the 33-mer peptide and shorter fragments containing overlapping T cell epitopes.

Antibody Production

The immune system produces antibodies against alpha-gliadins, including IgA and IgG classes. These antibodies, known as anti-gliadin antibodies (AGAs), are found in the sera of celiac disease patients. 

For example, Alpha-Beta Gliadin IgA and IgG antibodies are produced in response to alpha and beta gliadins.

Innate Immune Activation

Alpha-gliadin peptides, particularly the p31-43 fragment, can trigger innate immune responses in the intestinal mucosa.  This activation leads to the production of pro-inflammatory cytokines and increased intestinal permeability.

Tissue Transglutaminase (tTG) Involvement

tTG plays a crucial role in enhancing the immunogenicity of alpha-gliadin peptides by deamidating specific glutamine residues to glutamic acid.  This modification increases the binding affinity of these peptides to HLA-DQ2/8 molecules.

Differential Toxicity Among Wheat Genomes

Alpha-gliadins from different wheat genomes (A, B, and D) contain varying combinations of T cell stimulatory epitopes.  The D genome-derived alpha-gliadins are generally considered the most immunogenic.

What is Alpha-Gliadin IgA?

Alpha-gliadin IgA antibodies are a specific class of immunoglobulins produced by the immune system in response to alpha-gliadin, a component of gluten proteins found in wheat and related grains. 

While commonly associated with celiac disease, alpha-gliadin IgA antibodies can also be found in some individuals without enteropathy, indicating their presence in other forms of gluten sensitivity.  [3., 16.]

The detection of these antibodies is often part of a comprehensive evaluation for gluten-related disorders, although it is not considered a definitive diagnostic test on its own. 

Historically, anti-gliadin antibody (AGA) tests were used to diagnose gluten-driven enteropathy, but newer tests assessing for antibodies against deamidated gluten peptides and tissue transglutaminase have shown improved performance.  [1., 3.] 

However, they may still be used in conjunction with other tests.  

However, it's crucial to note that diagnosis of celiac disease or other gluten-related disorders typically requires a combination of serological tests, genetic testing, and often intestinal biopsy, along with clinical evaluation by a healthcare professional.

Role of Alpha-Gliadin IgA in Celiac Disease and Non-Celiac Gluten Sensitivity

Alpha-Gliadin IgA Antibodies in Celiac Disease  [3., 16.]

In celiac disease (CD), the production of IgA antibodies against gliadin, including alpha-gliadin, is a significant aspect of the immune response to gluten ingestion. 

The pathogenesis of CD involves both innate and adaptive immune responses.  The adaptive immune response is primarily mediated by the presentation of deamidated gliadin peptides to T cells by HLA-DQ2 or HLA-DQ8 molecules, which leads to the activation of T-helper cells. 

These activated T-helper cells then stimulate B cells to produce various antibodies, including IgA and IgG against gliadin and tissue transglutaminase (tTG).

The production of IgA antibodies against gliadin (AGA-IgA) occurs as part of this adaptive immune response.  These antibodies are among the first serological markers to appear in CD patients. 

However, AGA-IgA is not highly specific to CD, as these antibodies can also be found in other conditions and in healthy individuals.  

Therefore, while AGA-IgA can indicate an immune response to gliadin, it is not solely definitive for diagnosing CD without the presence of other more specific markers like tTG or endomysial antibodies (EmA).

In CD, gliadin peptides also trigger an innate immune response, which includes the release of interleukin-15 (IL-15) and other pro-inflammatory cytokines, leading to mucosal damage. This dual immune response—both innate and adaptive—contributes to the characteristic intestinal damage seen in CD, including villous atrophy and crypt hyperplasia.

Alpha-Gliadin IgA Antibodies in Non-Celiac Gluten Sensitivity  [3., 17.]

In Non-Celiac Gluten Sensitivity (NCGS), the presence of anti-gliadin antibodies (AGA) of the IgA class is reported, but their diagnostic value is also unclear.  

In NCGS, the prevalence of AGA-IgA is generally lower compared to CD.  Studies have shown that the prevalence of AGA-IgA in NCGS ranges from 6% to 40%.  [3.]  However, these antibodies are not as specific or sensitive for NCGS as they are for CD.

The presence of AGA-IgA in NCGS patients is not considered a reliable diagnostic marker due to its low sensitivity and specificity.  The positivity rates among NCGS patients compared to healthy controls or other conditions do not show significant differences that would make AGA-IgA a useful standalone diagnostic tool for NCGS.

Other antibodies may be necessary for a more complete clinical picture.  

In CD, the presence of IgA antibodies, particularly against tissue transglutaminase (tTG) and deamidated gliadin peptides (DGP), is more specific and serves as a key part of the diagnostic criteria. 

In contrast, NCGS lacks such specific serological markers, making the diagnosis more challenging and primarily based on symptom resolution upon gluten withdrawal and reappearance upon gluten challenge.

Effect of Gluten-Free Diet (GFD) on IgA Antibodies in Celiac Disease and NCGS  [3., 17.] 

In studies examining the effect of a GFD, it was found that AGA-IgA levels in NCGS patients decrease significantly after gluten withdrawal, indicating a positive response to the diet. 

However, this decrease is more variable and less consistent compared to CD patients.  These antibodies tend to persist in CD patients despite long-term withdrawal from gluten.  

Signs and Symptoms of Celiac Disease  [8., 11.] 

Digestive Symptoms:

• Chronic diarrhea or constipation

• Abdominal pain or cramps 

• Bloating and gas 

• Nausea and vomiting

• Pale, foul-smelling, fatty stools 

Other Symptoms:

• Weight loss

• Fatigue and weakness 

• Anemia (iron deficiency) 

• Bone/joint pain, osteoporosis 

• Itchy, blistery skin rash (dermatitis herpetiformis) 

• Mouth ulcers 

• Headaches

• Tingling/numbness in hands and feet

• Infertility, miscarriage 

Symptoms in Children

• Failure to thrive in infants  

• Delayed growth and puberty 

• Irritability 

• Damaged tooth enamel

• Neurological issues like ADHD, learning disabilities 

Laboratory Testing for Alpha-Gliadin IgA

Test Information, Sample Collection and Special Preparation

Testing for the alpha-gliadin IgA typically requires a blood sample to assess for IgA antibodies against this peptide, which often requires a venipuncture.  IgG and IgA antibodies are often assessed together to determine whether the individual has mounted an immune response against this gluten-based peptide.

A positive finding in this test should be accompanied or followed with additional assessment including IgA and IgG Anti-Tissue Transglutaminase antibodies and other serological markers.  

Interpretation of the Alpha-Gliadin IgA Test

Optimal Levels for Alpha-Gliadin IgA Antibodies

The presence of IgA antibodies against alpha-gliadin indicates that an immune response has been mounted against these peptides.

Optimal levels of these antibodies are undetectable, or very low.  

For reference, one lab reports the following recommended ranges for alpha-gliadin IgA antibodies:  [14.] 

Gliadin IgA <20 U

Clinical Significance of Elevated Alpha-Gliadin IgA Antibodies

Elevated alpha-gliadin IgA antibodies signal a positive immune response against this gluten-based peptide.  

Because some individuals can test positive for alpha-gliadin antibodies with no symptoms, results should be interpreted in the context of an individual’s symptom picture.

This may or may not be caused by celiac disease, although further assessment for celiac disease may be warranted, especially if anti-tTG antibodies are also elevated.  [3.]

Alpha-Gliadin IgA Related Biomarkers to Test

In addition to Alpha-Gliadin IgA antibodies, several other biomarkers are commonly tested in the evaluation of celiac disease and gluten-related disorders.

Tissue Transglutaminase (tTG) Antibodies

Tissue transglutaminase (tTG) is an enzyme that catalyzes the deamidation of gliadin peptides, increasing their immunogenicity.  In individuals with HLA-DQ2 or HLA-DQ8 genes, the deamidated gluten peptides are presented to CD4+ T cells, triggering an adaptive immune response.  [6.] 

This leads to the activation of both T cells and B cells, resulting in the production of antibodies against gluten (anti-gliadin) and tTG (anti-tTG).

Antibodies against tTG are highly specific for celiac disease and are the most widely used serological marker for diagnosis.  

Both IgA and IgG anti-tTG antibodies can be measured, although the IgA isotype is more often high (except in the setting of IgA depletion or deficiency), so an anti-tTG IgA antibody test is considered the most sensitive and specific.  [7.] 

Deamidated Gliadin Peptide (DGP) Antibodies  [15.] 

Deamidated gliadin peptides (DGPs), including the Alpha-Gliadin-17-mer, are the primary targets of the autoimmune response in celiac disease.  

Levels of these antibodies may rise before anti-tTG antibodies, making them useful in the diagnosis of early celiac disease.  [10.] 

Antibodies against DGPs can be useful in diagnosing celiac disease, especially in patients with IgA deficiency or in children younger than 2 years old. 

Endomysial IgA Antibodies (EMA)  [4., 5.] 

Endomysial antibodies (EMA) are directed against the endomysial component of smooth muscle, which is rich in tTG. 

EMA testing has high specificity for celiac disease but lower sensitivity compared to anti-tTG and anti-DGP antibodies.  It is often used as a confirmatory test in conjunction with other serological markers. 

FAQ: Alpha-Gliadin IgA

What is Alpha-Gliadin?

Alpha-Gliadin is a component of gluten, which is a group of proteins found in wheat and related grains such as barley and rye.  It is one of the main proteins that can trigger an immune response in individuals with celiac disease.

What is IgA?

Immunoglobulin A (IgA) is a type of antibody that plays a crucial role in the immune function of mucous membranes.  It is found in high concentrations in the mucous linings of the gastrointestinal and respiratory tracts, as well as in saliva, tears, and breast milk.

What is Alpha-Gliadin IgA?

Alpha-Gliadin IgA refers to IgA antibodies that are produced in response to alpha-gliadin, a component of gluten.  These antibodies can be measured in blood tests.

Why is Alpha-Gliadin IgA Significant in Celiac Disease?

Alpha-Gliadin IgA is significant in celiac disease because the presence of these antibodies indicates an immune response to gluten.  Elevated levels of Alpha-Gliadin IgA antibodies are a marker for a gluten sensitivity.  

Historically they were a marker helping in the diagnosis of celiac disease, although recently other serology markers and biopsy are used in diagnosis of celiac disease.  

How is Alpha-Gliadin IgA Detected?

Alpha-Gliadin IgA is detected through a blood test.  This test measures the levels of IgA antibodies against alpha-gliadin to help diagnose celiac disease or monitor the response to a gluten-free diet.

What Does a Positive Alpha-Gliadin IgA Test Mean?

A positive Alpha-Gliadin IgA test indicates that the immune system is reacting to alpha-gliadin, suggesting that the individual may have developed an immune response to gluten.

Further testing, including additional serology as well as consideration of a biopsy of the small intestine, is usually required to confirm the diagnosis of celiac disease.

What Are the Symptoms of Celiac Disease?

Symptoms of celiac disease can vary but often include:

• Abdominal pain and bloating

• Chronic diarrhea or constipation

• Weight loss

• Fatigue

• Anemia

• Dermatitis herpetiformis (itchy skin rash)

• Nutritional deficiencies

How is Celiac Disease Diagnosed?

Celiac disease is typically diagnosed through a combination of blood tests and a biopsy of the small intestine to confirm damage to the intestinal villi.

What is the Treatment for Celiac Disease Related to Alpha-Gliadin IgA?

The primary treatment for celiac disease is a strict, lifelong gluten-free diet. This involves avoiding all foods that contain wheat, barley, rye, and their derivatives to prevent symptoms and intestinal damage.

Can Alpha-Gliadin IgA Levels Be Used to Monitor Treatment Success?

Alpha-Gliadin IgA levels can remain elevated in individuals with celiac disease; therefore, they are not always useful in monitoring treatment success.  

However, in individuals with non-celiac gluten sensitivity, IgA levels may decrease over time, making this an appropriate tool for monitoring treatment in this population.  

What Foods Contain Alpha-Gliadin?

Alpha-Gliadin is found in gluten-containing foods, which include products made from wheat, barley, and rye.  This includes bread, pasta, cereals, and many processed foods.

How Can One Avoid Alpha-Gliadin in Their Diet?

To avoid Alpha-Gliadin, individuals with celiac disease should follow a strict gluten-free diet. 

This involves reading food labels carefully, choosing naturally gluten-free foods (such as fruits, vegetables, and unprocessed meats), and selecting gluten-free alternatives for common gluten-containing foods.

Where Can I Find More Information About Alpha-Gliadin IgA and Celiac Disease?

For more information about Alpha-Gliadin IgA and celiac disease, consider consulting:

• Healthcare providers: Medical professionals can provide personalized advice and diagnosis.

• Celiac disease organizations: Websites of organizations such as the Celiac Disease Foundation and Beyond Celiac.

• Scientific literature: Research articles and reviews on gliadin peptides and their role in celiac disease.

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