Anti-gliadin antibodies
Encyclopedia
Antigliadin antibodies are produced in response to gliadin
, a prolamin
found in wheat
. In bread wheat it is encoded by three different allele
s, AA, BB, and DD. These alleles can produce slightly different gliadins, which can cause the body to produce different antibodies
. Some of these antibodies can detect protein
s in specific grass taxa such as Triticeae
(Triticeae glutens
), while others react sporadically with certain species in those taxa, or over many taxonomically defined grass tribe
s.
. It is directed
against the alpha/beta and gamma (α,β,γ) gliadins. It is also found in a number of patients who are not enteropathic. Some of these patients may have neuropathies that respond favorably to a gluten elimination diet. This is referred to as gluten-sensitive idiopathic neuropathy. Clinically these antibodies and IgG antibodies to gliadin are abbreviated as AGA.
, but is found at higher levels in patients with the IgA-less phenotype
. It is also associated with coeliac disease
and idiopathic gluten sensitivity.
Anti-gliadin antibodies are frequently found with anti-transglutaminase antibodies
.
-related conditions such as urticaria
, asthma
, and wheat-dependent exercise-induced anaphylaxis
. The target of the most allergenic antibodies is ω-5 gliadin, which is encoded by the Gli-1B gene found on the B haplome (Aegilops speltoides
derived) of wheat.
What is the relationship of gluten and anti-gliadin antibodies?. In gluten-sensitive
individuals AGA testing is a routinely used blood test for possible presence of coeliac disease, allergies or idiopathic phenomena. The measurement of AGA is done with ELISA
or radioimmunoassay. Such tests measure the level of AGA relative to a standard, such as a level of 10 = point which 85% of normal population falls below. Greater than 10 equals disease and a value of 3 is expected (mean).
Individuals who have coeliac disease may have values in excess of 200. There is the common expectation that removal of gluten results in the loss of AGA; however, since gluten is the target of the antibodies, that which would deplete them from the body, removal of gluten results in the benign circulation of antibodies. The half life of these antibodies is typically 120 days. Given an expected normal of 3 and assuming that the individual starts with a score of 203, we can predict the levels of AGA at various future time points. Based on these initial numbers, patients with very high
AGA values may take 2 years to return to the normal range.
Refractory coeliac diease (RCD). RCD or non-strict gluten-free diet are two causes of failure of AGA to return to normality on the GF diet. In the first instance lymphocytes may remain stimulated even though the antigen that originally stimulated them was removed from the diet.
biopsy diagnostic in performance.
that produces monoclonal antibodies
(Mab or MoAb). Mab can be expressed in culture or via ascites fluid
production to produce large amounts of a single antibody isoform.
Mab can be used to detect levels of gluten
in food products. Some of these antibodies can recognize only wheat
prolamin
s or very closely related grass seeds; others can detect antigen
s over broad taxa. The G12 antibody is the newest example, developed by the Spanish company Biomedal. It recognizes the toxic fraction of wheat, barley, rye and also of oat. The R5 sandwich assay is another such assay. This assay can recognize wheat, barley and rye, which makes it ideal for evaluating the presence of contaminants in gluten-free foods that do not contain oat. This antibody is a recommended testing protocol in a proposed revision of the Codex Alimentarius
.
The new standards came about in part because of new sensitive and specific testing procedures. These procedures are capable of detecting wheat or multiple cereals at concentrations as low as 1 part per million (PPM or 1 mg/kg). A new barley-sensitive ELISA called the R5 sandwich assay does not detect gluten in any of 25 pure oat varieties, but it does detect barley, wheat and rye.
Gliadin
Gliadin is a glycoprotein present in wheat and several other cereals within the grass genus Triticum. Gliadins are prolamins and are separated on the basis of electrophoretic mobility and isoelectric focusing.- Types :...
, a prolamin
Prolamin
Prolamins are a group of plant storage proteins having a high proline content and found in the seeds of cereal grains: wheat , barley , rye , corn , sorghum and as a minor protein, avenin in oats. They are characterised by a high glutamine and proline content and are generally soluble only in...
found in wheat
Wheat
Wheat is a cereal grain, originally from the Levant region of the Near East, but now cultivated worldwide. In 2007 world production of wheat was 607 million tons, making it the third most-produced cereal after maize and rice...
. In bread wheat it is encoded by three different allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
s, AA, BB, and DD. These alleles can produce slightly different gliadins, which can cause the body to produce different antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
. Some of these antibodies can detect protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s in specific grass taxa such as Triticeae
Triticeae
Triticeae is a tribe within the Pooideae subfamily of grasses that includes genera with many domesticated species. Major crop genera are found in this tribe including wheat , barley, and rye; crops in other genera include some for human consumption and others used for animal feed or rangeland...
(Triticeae glutens
Triticeae glutens
Triticeae glutens are seed storage proteins found in mature seeds of grass tribe Triticeae. Seed glutens of non-Triticeae plants have varieties of similar properties, but none singly can perform on a par with those of the Triticeae taxa, particularly the triticum species...
), while others react sporadically with certain species in those taxa, or over many taxonomically defined grass tribe
Tribe (biology)
In biology, a tribe is a taxonomic rank between family and genus. It is sometimes subdivided into subtribes.Some examples include the tribes: Canini, Acalypheae, Hominini, Bombini, and Antidesmeae.-See also:* Biological classification* Rank...
s.
Anti-gliadin IgA
This antibody is found in ~80% of patients with coeliac diseaseCoeliac disease
Coeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...
. It is directed
against the alpha/beta and gamma (α,β,γ) gliadins. It is also found in a number of patients who are not enteropathic. Some of these patients may have neuropathies that respond favorably to a gluten elimination diet. This is referred to as gluten-sensitive idiopathic neuropathy. Clinically these antibodies and IgG antibodies to gliadin are abbreviated as AGA.
Anti-gliadin IgG
The IgG antibody is similar to AGA IgAIGA
Iga or IGA may stand for:-Given name:* a female given name of Polish origin. The name originates from the female given name Jadwiga and stands for gia,or gina in the USA....
, but is found at higher levels in patients with the IgA-less phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
. It is also associated with coeliac disease
Coeliac disease
Coeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...
and idiopathic gluten sensitivity.
Anti-gliadin antibodies are frequently found with anti-transglutaminase antibodies
Anti-transglutaminase antibodies
Anti-transglutaminase antibodies are autoantibodies against the transglutaminase protein. Antibodies serve an important role in the immune system by detecting cells and substances that the rest of the immune system then eliminates. These cells and substance can be foreign and also can be producd...
.
Anti-gliadin IgE
The IgE antibodies are more typically found in allergyAllergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
-related conditions such as urticaria
Urticaria
Urticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
, asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, and wheat-dependent exercise-induced anaphylaxis
Exercise-induced anaphylaxis
Exercise-induced anaphylaxis is a syndrome in which the symptoms of anaphylaxis occur related to exercise.In some incidents, individuals experienced anaphylaxis only after combination exposure to a triggering agent and increased physical activity shortly after the ingestion of the triggering agent...
. The target of the most allergenic antibodies is ω-5 gliadin, which is encoded by the Gli-1B gene found on the B haplome (Aegilops speltoides
Aegilops speltoides
Aegilops speltoides is an edible plant in the Poaceae family native to Southeastern Europe and Western Asia, which is often used for animal feed, and it has grown in cultivated beds...
derived) of wheat.
Anti-gliadin antibodies and the gluten-free diet
| Days on GF diet | AGA | |
| 0 | 203 | |
| 7 (1 wk) | 195 | |
| 30 (1 mo.) | 171 | |
| 61 (2 mo.) | 144 | |
| 91 (3 mo) | 121 | |
| 122 (4 mo) | 101 | |
| 183 (6 mo) | 72 | |
| 274 (9 mo) | 44 | |
| 365 (1 yr) | 27 | |
| 548 (18 mo) | 11 | |
| 730 (2 yr) | 6 | |
| AGA values below 10 (black) are normal | ||
What is the relationship of gluten and anti-gliadin antibodies?. In gluten-sensitive
Gluten sensitivity
Gluten sensitivity belongs to a spectrum of disorders in which gluten has an adverse effect on the body. It can be defined as a non-allergic and non-autoimmune condition in which the consumption of gluten can lead to symptoms similar to those observed in coeliac disease or wheat allergy .Gluten...
individuals AGA testing is a routinely used blood test for possible presence of coeliac disease, allergies or idiopathic phenomena. The measurement of AGA is done with ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...
or radioimmunoassay. Such tests measure the level of AGA relative to a standard, such as a level of 10 = point which 85% of normal population falls below. Greater than 10 equals disease and a value of 3 is expected (mean).
Individuals who have coeliac disease may have values in excess of 200. There is the common expectation that removal of gluten results in the loss of AGA; however, since gluten is the target of the antibodies, that which would deplete them from the body, removal of gluten results in the benign circulation of antibodies. The half life of these antibodies is typically 120 days. Given an expected normal of 3 and assuming that the individual starts with a score of 203, we can predict the levels of AGA at various future time points. Based on these initial numbers, patients with very high
AGA values may take 2 years to return to the normal range.
Refractory coeliac diease (RCD). RCD or non-strict gluten-free diet are two causes of failure of AGA to return to normality on the GF diet. In the first instance lymphocytes may remain stimulated even though the antigen that originally stimulated them was removed from the diet.
Diagnostic serology
Anti-gliadin antibodies were one of the first serological markers for coeliac disease. Problematic with AGA is the typical sensitivity and specificity was about 85%. Gliadin peptides which are synthesized as the deamidated form have much higher sensitivity and specificity, creating 2 serological tests for CD that approachbiopsy diagnostic in performance.
Uses of Anti-gliadin antibodies in testing
Antigliadin antibodies can be generated in mice or rabbits by immunizing whole purified gliadins, proteolytic fragments of gliadin, or synthetic peptides that represent epitopes of gliadin. After developing an immune response, B-cells from mice can be fused with immortalizing cells to form a hybridomaHybridoma
Hybridoma technology is a technology of forming hybrid cell lines by fusing a specific antibody-producing B cell with a myeloma cell that is selected for its ability to grow in tissue culture and for an absence of antibody chain synthesis...
that produces monoclonal antibodies
Monoclonal antibodies
Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....
(Mab or MoAb). Mab can be expressed in culture or via ascites fluid
Ascites
Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...
production to produce large amounts of a single antibody isoform.
Mab can be used to detect levels of gluten
Gluten
Gluten is a protein composite found in foods processed from wheat and related grain species, including barley and rye...
in food products. Some of these antibodies can recognize only wheat
Wheat
Wheat is a cereal grain, originally from the Levant region of the Near East, but now cultivated worldwide. In 2007 world production of wheat was 607 million tons, making it the third most-produced cereal after maize and rice...
prolamin
Prolamin
Prolamins are a group of plant storage proteins having a high proline content and found in the seeds of cereal grains: wheat , barley , rye , corn , sorghum and as a minor protein, avenin in oats. They are characterised by a high glutamine and proline content and are generally soluble only in...
s or very closely related grass seeds; others can detect antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s over broad taxa. The G12 antibody is the newest example, developed by the Spanish company Biomedal. It recognizes the toxic fraction of wheat, barley, rye and also of oat. The R5 sandwich assay is another such assay. This assay can recognize wheat, barley and rye, which makes it ideal for evaluating the presence of contaminants in gluten-free foods that do not contain oat. This antibody is a recommended testing protocol in a proposed revision of the Codex Alimentarius
Codex Alimentarius
The Codex Alimentarius is a collection of internationally recognized standards, codes of practice, guidelines and other recommendations relating to foods, food production and food safety. Its name derives from the Codex Alimentarius Austriacus...
.
The new standards came about in part because of new sensitive and specific testing procedures. These procedures are capable of detecting wheat or multiple cereals at concentrations as low as 1 part per million (PPM or 1 mg/kg). A new barley-sensitive ELISA called the R5 sandwich assay does not detect gluten in any of 25 pure oat varieties, but it does detect barley, wheat and rye.