Alpha-Gliadin + Gliadin Toxic Peptide

Alpha-gliadin is a gluten protein found in wheat and related grains, containing peptide sequences toxic to individuals with celiac disease. 

Notably, the 33-mer fragment from alpha-gliadins includes several celiac-toxic epitopes that bind to HLA-DQ2 and HLA-DQ8 molecules, triggering both adaptive and innate immune responses. 

This interaction leads to inflammation and structural changes in the small intestinal mucosa. 

Gliadin toxic peptides, including the 33-mer fragment and the alpha-gliadin 17-mer peptide, are significant in celiac disease for their role in stimulating immune responses.  These peptides can cross the intestinal barrier, interact with immune cells, and induce harmful effects even without an adaptive immune response. 

Understanding these mechanisms is essential for developing new therapeutic approaches and improving disease management.

What are Alpha-Gliadin + Gliadin Toxic Peptides?

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.  [10.] 

For example, the 33-mer fragment from the N-terminal part of alpha-gliadins includes several celiac disease-toxic epitopes which bind well with HLA-DQ2 and HLA-DQ8 molecules and are recognized by gluten-sensitive T cells.  [10.] 

This binding triggers both adaptive and innate immune responses, leading to inflammation and structural changes in the small intestinal mucosa of celiac patients.

Gliadin toxic peptides are the specific fragments of gliadin proteins, including alpha-gliadin, found in wheat and related grains.  Gliadin toxic peptides can induce harmful effects in individuals with celiac disease or gluten sensitivity, even without triggering an adaptive immune response. 

They may promote the release of zonulin, stimulating a leaky gut pathogenesis.  [17.] 

Through complex interactions with enzymes such as tissue transglutaminase as well as with the immune system, the toxicity of these peptides may be altered.  [10., 18.] 

Alpha-Gliadin Peptide 31-43

Alpha-gliadin peptide 31-43 is considered an important gliadin toxic peptide responsible for triggering the innate, or non-T cell-mediated, immune response in celiac disease patients.  [18.] 

Cytotoxicity of Alpha-Gliadin Peptide 31-43 

Peptide 31-43 is identified as toxic to epithelial cells, including Caco2 cells, despite not being a substrate for tissue transglutaminase (tTG).  This distinguishes it from other toxic peptides, which often require deamidation by tTG to exert their effects.

Mechanism of Toxicity of Alpha-Gliadin Peptide 31-43

The toxicity of peptide 31-43 is not associated with apoptosis or necrosis, as indicated by flow cytometry analyses.  This suggests that the peptide inhibits cell growth through a different mechanism, which remains unclear.

It can rapidly enter cells, although how it does so is also unclear.  [14.] 

Peptide 31-43 does not affect tTG activity.  This sets it apart from other peptides, whose toxicity is related to their interactions with tTG.  [18.] 

The unique properties of peptide 31-43, particularly its ability to induce toxicity without involving tTG, highlight the complexity of gliadin peptides in CD pathogenesis.

The 33-mer Peptide  [1., 9., 13.] 

The 33-mer peptide, derived from alpha-gliadin, is another gliadin toxic peptide and a potent T-cell stimulator.

This peptide is notable for its resistance to gastrointestinal digestion and high proline and glutamine content, allowing it to adopt a polyproline II structure and form oligomers and fibrils.  

These properties enable the 33-mer peptide to cross the intestinal barrier, where it interacts with immune cells and activates the innate immune response via Toll-like receptors. 

After deamidation by tissue transglutaminase, it binds strongly to HLA-DQ2/DQ8 molecules on antigen-presenting cells, thereby activating the adaptive immune response. 

This peptide's ability to resist digestion and accumulate in the lamina propria of celiac patients is crucial in sustaining the inflammatory response characteristic of celiac disease.

Alpha-Gliadin-17-mer Peptide  [1., 2., 5.] 

The alpha-gliadin 17-mer peptide is a truncated form of the 33-mer gliadin toxic peptide and is highly potent in stimulating intestinal T cell responses in HLA-DQ2+ celiac patients. 

It plays a significant role in celiac disease by triggering both adaptive and innate immune responses, contributing to inflammation and structural changes in the small intestine. 

This peptide is deamidated by tissue transglutaminase, allowing it to bind strongly to HLA-DQ2/DQ8 molecules on antigen-presenting cells, leading to a pro-inflammatory Th1 response. 

Its strong immunogenicity and specificity make it a key target for developing peptide-based therapies aimed at inducing immune tolerance to gluten. 

The alpha-gliadin 17-mer peptide's role in activating immune pathways and causing enterocyte proliferation highlights its importance in the pathogenesis of celiac disease, making it crucial for the development of new therapeutic approaches.

Signs and Symptoms of Celiac Disease  [8., 12.] 

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 and Gliadin Toxic Peptides

Test Information, Sample Collection and Special Preparation

Testing for Alpha-Gliadin + Gliadin Toxic Peptides typically requires a blood sample to assess for antibodies against this peptide, which often requires a venipuncture.  IgG and IgA antibodies may be assessed to determine whether the individual has mounted an immune response against these gluten-based peptides.

Interpretation of the Alpha-Gliadin and Gliadin Toxic Peptides Test

Optimal Levels for Alpha-Gliadin and Gliadin Toxic Peptide Antibodies

The presence of antibodies against alpha-gliadin and gliadin toxic peptides indicates that an immune response has been mounted against these peptides, and also indicates the likely presence of intestinal inflammation.  

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

For reference, one lab reports the following recommended ranges for alpha-gliadin and gliadin toxic peptides antibodies:  

Alpha Gliadin + Gliadin Toxic Peptide IgG 0.2-1.4 ELISA index  [15.] 

Gliadin Toxic Peptide IgG 0.1-1.7 ELISA index  [16.] 

Gliadin Toxic Peptide IgA 0.1-1.5 ELISA index  [16.] 

These results are determined according to the mean antibody levels found in healthy individuals, +/- 2 standard deviations.  [16.] 

Clinical Significance of Elevated Alpha-Gliadin and Gliadin Toxic Peptide Antibodies

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

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.

Additionally, elevated gliadin toxic peptides may also be present with leaky gut, so further assessment for leaky gut may be warranted.  [17.] 

In addition to Alpha-Gliadin-17-mer antibodies, several other biomarkers are commonly tested in the evaluation of celiac disease and gluten-related disorders.

Alpha-Gliadin and Gliadin Toxic Peptide Related Biomarkers to Test

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  [19.] 

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.  [11.] 

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)  [3., 4.] 

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 and Gliadin Toxic Peptides

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 responsible for the elastic properties of dough and bread.

What are Gliadin Toxic Peptides?

Gliadin Toxic Peptides are specific sequences of amino acids derived from gliadin proteins. 

These peptides can trigger immune responses in individuals with celiac disease, leading to inflammation and damage in the small intestine.

What Is the Significance of Alpha-Gliadin and Gliadin Toxic Peptides in Celiac Disease?

Alpha-Gliadin and Gliadin Toxic Peptides contain epitopes that are recognized by the immune system of individuals with celiac disease. 

When these peptides are ingested, they can provoke an autoimmune response that damages the intestinal lining, leading to the symptoms and complications of celiac disease.

How Are Alpha-Gliadin and Gliadin Toxic Peptides Detected?

Detection of Alpha-Gliadin and Gliadin Toxic Peptides is typically done through immunological assays such as enzyme-linked immunosorbent assays (ELISA), which can identify the presence of antibodies against these peptides in the blood of individuals with celiac disease.

What Are the Symptoms of Celiac Disease Triggered by Alpha-Gliadin and Gliadin Toxic Peptides?

Symptoms of celiac disease can vary widely but often include:

• Abdominal pain and bloating

• Chronic diarrhea or constipation

• Weight loss

• Fatigue

• Anemia

• Dermatitis herpetiformis (itchy skin rash)

• Nutritional deficiencies

How Can Celiac Disease be Diagnosed?

Celiac disease is diagnosed through a combination of blood tests and a biopsy of the small intestine.  Blood tests look for specific antibodies against gliadin peptides, while a biopsy can show damage to the intestinal villi.

What is the treatment for reactions caused by Alpha-Gliadin and Gliadin Toxic Peptides?

The primary treatment for celiac disease and reactions caused by Alpha-Gliadin and Gliadin Toxic Peptides is a strict, lifelong gluten-free diet.  This involves avoiding all foods that contain wheat, barley, rye, and their derivatives.

Can Alpha-Gliadin and Gliadin Toxic Peptides be Used in Research?

Yes, Alpha-Gliadin and Gliadin Toxic Peptides are commonly used in research to study the immune response in celiac disease. 

They help in understanding the pathogenesis of the disease and in developing potential therapeutic interventions.

What Foods Contain Alpha-Gliadin and Gliadin Toxic Peptides?

Alpha-Gliadin and Gliadin Toxic Peptides are 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 and Gliadin Toxic Peptides in Their Diet?

To avoid Alpha-Gliadin and Gliadin Toxic Peptides, 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, Gliadin Toxic Peptides, and Celiac Disease?

For more information about Alpha-Gliadin, Gliadin Toxic Peptides, 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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