Alpha-Gliadin IgM

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 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. 

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.  These antibodies, known as anti-gliadin antibodies (AGAs), are found in the sera of celiac disease patients. 

For example, Alpha-Beta Gliadin 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.

Clinical Significance of Alpha-Gliadin IgM Antibodies

The significance of antibodies against gliadin has been explored for decades; increasingly, antibodies against other compounds are used for the diagnosis and monitoring of celiac disease.  

Alpha-gliadin IgM antibodies have shown inconsistent clinical value.  

In one study from 1981, the authors investigated the presence of IgM antibodies against gliadin using two different methods: an immunofluorescent (IF) test and a mixed reverse (solid-phase) passive antiglobulin hemadsorption (MRsPAH) test.  [17.] 

While they could detect low levels of IgM antibodies against gliadin in some sera, these antibodies were not specific to any particular disease and did not correlate with clinical features in their subjects, making them of limited clinical relevance in the context of celiac disease and other gastrointestinal diseases.  [17.] 

Another study failed to show a correlation to severity of inflammatory bowel disease and systemic antibodies including IgM in monozygotic twins, although the correlations with celiac disease were not explored.  [22.] 

However, another study utilized an adaptation of the enzyme-linked immunosorbent assay (ELISA) system to assess antibodies, including IgM, to alpha-gliadin, crude gliadin, and casein.  [21.] 

It was found that alpha-gliadin was the only antigen consistently able to differentiate patients with untreated celiac disease from normal controls and patients with chronic inflammatory bowel disease.  [21.] 

The mean assay index for patients with untreated celiac disease was significantly higher compared to normal controls and patients with chronic inflammatory bowel disease.  [21.] 

Another article discusses anti-gliadin IgM production in the GI tract as a driver of intestinal inflammation and autoimmune processes.  The author states the following:  [19.] 

Increased antigen uptake in the intestine precedes the onset of many immunologically mediated GI diseases.  This uptake can lead to the production of serum immunoglobulins, including IgM, to food antigens such as gliadin.

When tight junctions in the intestinal barrier are damaged, large antigenic molecules (like gliadin) can enter the submucosa and regional lymph nodes.  This triggers the immune system to produce antibodies, including significantly elevated levels of IgG, IgM, and IgA specific to occludin/zonulin, actomyosin, and bacterial LPS.  [19.]

The author states that the presence of these specific antibodies (IgG, IgM, and IgA) in the blood serves as an indicator of increased intestinal permeability and subsequent immune system activation.  [19., 20.]  This is particularly relevant in autoimmune diseases where such permeability and immune responses play a pivotal role in disease progression. 

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 IgM

Test Information, Sample Collection and Special Preparation

Testing for the alpha-gliadin IgM typically requires a blood sample to assess for IgM antibodies against this peptide, which often requires a venipuncture.  

IgG and IgA antibodies are most commonly assessed, and are often ordered together to determine whether the individual has mounted an immune response against this gluten-based peptide.  IgM antibodies may also be included.

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 IgM Test

Optimal Levels for Alpha-Gliadin IgM Antibodies

The presence of IgM 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 IgM antibodies:  [14.] 

Alpha-Gliadin IgA + IgM 0.2-2.0 ELISA Index

Clinical Significance of Elevated Alpha-Gliadin IgM Antibodies

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

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 IgM Related Biomarkers to Test

In addition to Alpha-Gliadin IgM 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 IgM

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 primary proteins that can trigger an immune response in individuals with celiac disease.

What is IgM?

Immunoglobulin M (IgM) is a type of antibody that is produced by the immune system as an early response to infections.  It is the first antibody to be made by the body when fighting a new infection and is mainly found in the blood and lymphatic fluid.

What is Alpha-Gliadin IgM?

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

How is Alpha-Gliadin IgM Detected?

Alpha-Gliadin IgM is detected through a blood test.  This test measures the levels of IgM antibodies against alpha-gliadin to help diagnose celiac disease or other gluten-related disorders.

What Does a Positive Alpha-Gliadin IgM Test Mean?

A positive Alpha-Gliadin IgM test indicates that the immune system is reacting to alpha-gliadin, or possibly is cross-reacting to a similar compound.  Further testing, including additional bloodwork and possibly a biopsy of the small intestine, is usually required to confirm the diagnosis.

What Are the Symptoms of Celiac Disease?

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 is Celiac Disease Diagnosed?

Celiac disease is 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 IgM?

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.

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 Celiac Disease?

For more information about Alpha-Gliadin IgM 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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