Anti-gliadin antibodies

Last updated
Antibody(s)
Anti-gliadin
Common Antibody characteristics
Antigen SourceTriticum aestivum
Isoform specific
antibody characteristics
Antigen
Isoform		α/β-gliadin
Antigen GeneGli-X2
Affected Organ(s)Intestine (Small)
Also AffectedEpithelial extracellular matrix
Associated
Disease(s)		 Coeliac disease
Antibody classIgA, IgG
DQ2.5
HLA associations DQ8
DQ2.2/DQ7.5
Antigen
Isoform		γ-gliadin
Antigen GeneGli-X3
Affected Organ(s)(See α/β-gliadin)
Associated
Disease(s)		 Coeliac disease
Antibody classIgA, IgG
DQ2.5
HLA associationsDQ8
DQ2.2/DQ7.5
Antigen
Isoform		ω-gliadin
Biological source& Aegilops speltoides
Antigen GeneGli-B1
Affected Organ(s)Vascular, Respiratory
Affected Tissue(s) Serum, Dermis
Affected Cells(s) Mast cells, Eosinophils
Associated
Disease(s)		 EIA, Baker's Allergy
Antibody classIgE

Anti-gliadin antibodies are produced in response to gliadin, a prolamin found in wheat. In bread wheat it is encoded by three different alleles, 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 proteins 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 tribes.

Contents

Subtypes

Anti-gliadin IgA

This antibody is found in ~80% of patients with coeliac disease. [1] [2] It is directed against the alpha/beta and gamma (α,β,γ) gliadins. [3] 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. [4] Clinically these antibodies and IgG antibodies to gliadin are abbreviated as AGA.

Anti-gliadin IgG

The IgG antibody is similar to AGA IgA, but is found at higher levels in patients with the IgA-less phenotype. It is also associated with coeliac disease and non-celiac gluten sensitivity. [5] [6] [7]

Anti-gliadin antibodies are frequently found with anti-transglutaminase antibodies.

Anti-gliadin IgE

The IgE antibodies are more typically found in allergy-related conditions such as urticaria, asthma, and wheat-dependent exercise-induced anaphylaxis. The target of the most allergenic antibodies is ω-5 gliadin, [8] which is encoded by the Gli-1B gene found on the B haplome ( Aegilops speltoides derived) of wheat. [9]

Gluten-free diet

Loss of AGA on GF diet
Days on GF dietAGA
0203
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 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)[ citation needed ].

Individuals who have coeliac disease may have values in excess of 200[ citation needed ]. 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 disease (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 approach biopsy diagnostic in performance. [10] [11]

Uses in testing

Anti-gliadin 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 hybridoma 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 prolamins or very closely related grass seeds; others can detect antigens over broad taxa. The G12 antibody [12] is the newest example which detects the most immunotoxic fragment, a 33-mer peptide from α-2 gliadin; available from Romer Laboratories and the Spanish company Biomedal. It recognizes the toxic fraction of wheat, barley, rye and also of oat. [13]

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. [14] 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. [15]

Related Research Articles

<span class="mw-page-title-main">Gluten</span> Group of cereal grain proteins

Gluten is a structural protein naturally found in certain cereal grains. Although "gluten" often only refers to wheat proteins, in medical literature it refers to the combination of prolamin and glutelin proteins naturally occurring in all grains that have been proven capable of triggering celiac disease. These include any species of wheat, barley, rye and some oat cultivars, as well as any cross hybrids of these grains. Gluten makes up 75–85% of the total protein in bread wheat.

<span class="mw-page-title-main">Oat</span> Cool weather staple grain, animal feed

The oat, sometimes called the common oat, is a species of cereal grain grown for its seed, which is known by the same name. While oats are suitable for human consumption as oatmeal and rolled oats, one of the most common uses is as livestock feed. Oats are a nutrient-rich food associated with lower blood cholesterol when consumed regularly.

<span class="mw-page-title-main">Coeliac disease</span> Autoimmune disorder that results in a reaction to gluten

Coeliac disease or celiac disease is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barley. Classic symptoms include gastrointestinal problems such as chronic diarrhoea, abdominal distention, malabsorption, loss of appetite, and among children failure to grow normally. This often begins between six months and two years of age. Non-classic symptoms are more common, especially in people older than two years. There may be mild or absent gastrointestinal symptoms, a wide number of symptoms involving any part of the body, or no obvious symptoms. Coeliac disease was first described in childhood; however, it may develop at any age. It is associated with other autoimmune diseases, such as Type 1 diabetes mellitus and Hashimoto's thyroiditis, among others.

<span class="mw-page-title-main">Gluten-free diet</span> Diet excluding proteins found in wheat, barley, and rye

A gluten-free diet (GFD) is a nutritional plan that strictly excludes gluten, which is a mixture of proteins found in wheat, as well as barley, rye, and oats. The inclusion of oats in a gluten-free diet remains controversial, and may depend on the oat cultivar and the frequent cross-contamination with other gluten-containing cereals.

Food intolerance is a detrimental reaction, often delayed, to a food, beverage, food additive, or compound found in foods that produces symptoms in one or more body organs and systems, but generally refers to reactions other than food allergy. Food hypersensitivity is used to refer broadly to both food intolerances and food allergies.

<span class="mw-page-title-main">Gliadin</span>

Gliadin is a class of proteins present in wheat and several other cereals within the grass genus Triticum. Gliadins, which are a component of gluten, are essential for giving bread the ability to rise properly during baking. Gliadins and glutenins are the two main components of the gluten fraction of the wheat seed. This gluten is found in products such as wheat flour. Gluten is split about evenly between the gliadins and glutenins, although there are variations found in different sources.

<span class="mw-page-title-main">Wheat allergy</span> Medical condition

Wheat allergy is an allergy to wheat which typically presents itself as a food allergy, but can also be a contact allergy resulting from occupational exposure. Like all allergies, wheat allergy involves immunoglobulin E and mast cell response. Typically the allergy is limited to the seed storage proteins of wheat. Some reactions are restricted to wheat proteins, while others can react across many varieties of seeds and other plant tissues. Wheat allergy is rare. Prevalence in adults was found to be 0.21% in a 2012 study in Japan.

<span class="mw-page-title-main">Triticeae</span> Tribe of grasses

Triticeae is a botanical tribe within the subfamily Pooideae of grasses that includes genera with many domesticated species. Major crop genera found in this tribe include wheat, barley, and rye; crops in other genera include some for human consumption, and others used for animal feed or rangeland protection. Among the world's cultivated species, this tribe has some of the most complex genetic histories. An example is bread wheat, which contains the genomes of three species with only one being a wheat Triticum species. Seed storage proteins in the Triticeae are implicated in various food allergies and intolerances.

<span class="mw-page-title-main">Triticeae glutens</span> Seed storage protein in mature wheat seeds

Gluten is the seed storage protein in mature wheat seeds. It is the sticky substance in bread wheat which allows dough to rise and retain its shape during baking. The same, or very similar, proteins are also found in related grasses within the tribe Triticeae. Seed glutens of some non-Triticeae plants have similar properties, but none can perform on a par with those of the Triticeae taxa, particularly the Triticum species. What distinguishes bread wheat from these other grass seeds is the quantity of these proteins and the level of subcomponents, with bread wheat having the highest protein content and a complex mixture of proteins derived from three grass species.

<span class="mw-page-title-main">Gluten-related disorders</span> Set of diseases caused by gluten exposure

Gluten-related disorders is the term for the diseases triggered by gluten, including celiac disease (CD), non-celiac gluten sensitivity (NCGS), gluten ataxia, dermatitis herpetiformis (DH) and wheat allergy. The umbrella category has also been referred to as gluten intolerance, though a multi-disciplinary physician-led study, based in part on the 2011 International Coeliac Disease Symposium, concluded that the use of this term should be avoided due to a lack of specificity.

Gluten-sensitive enteropathy–associated conditions are comorbidities or complications of gluten-related gastrointestinal distress. GSE has key symptoms typically restricted to the bowel and associated tissues; however, there are a wide variety of associated conditions. These include bowel disorders, eosinophilic gastroenteritis and increase with coeliac disease (CD) severity. With some early onset and a large percentage of late onset disease, other disorders appear prior to the coeliac diagnosis or allergic-like responses markedly increased in GSE. Many of these disorders persist on a strict gluten-free diet, and are thus independent of coeliac disease after triggering. For example, autoimmune thyroiditis is a common finding with GSE.

Anti-transglutaminase antibodies (ATA) 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 substances can be foreign and also can be produced by the body. Antibodies against the body's own products are called autoantibodies. Autoantibodies can sometimes errantly be directed against healthy portions of the organism, causing autoimmune diseases.

<span class="mw-page-title-main">HLA-DQ2</span>

HLA-DQ2 (DQ2) is a serotype group within HLA-DQ (DQ) serotyping system. The serotype is determined by the antibody recognition of β2 subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ2 are encoded by the HLA-DQB1*02 allele group. This group currently contains two common alleles, DQB1*0201 and DQB1*0202. HLA-DQ2 and HLA-DQB1*02 are almost synonymous in meaning. DQ2 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively.

<span class="mw-page-title-main">Enteropathy-associated T-cell lymphoma</span> Complication of coeliac disease

Enteropathy-associated T-cell lymphoma (EATL), previously termed enteropathy-associated T-cell lymphoma, type I and at one time termed enteropathy-type T-cell lymphoma (ETTL), is a complication of coeliac disease in which a malignant T-cell lymphoma develops in areas of the small intestine affected by the disease's intense inflammation. While a relatively rare disease, it is the most common type of primary gastrointestinal T-cell lymphoma.

Oat sensitivity represents a sensitivity to the proteins found in oats, Avena sativa. Sensitivity to oats can manifest as a result of allergy to oat seed storage proteins either inhaled or ingested. A more complex condition affects individuals who have gluten-sensitive enteropathy in which there is an autoimmune response to avenin, the glutinous protein in oats similar to the gluten within wheat. Sensitivity to oat foods can also result from their frequent contamination by wheat, barley, or rye particles.

The immunochemistry of Triticeae glutens is important in several inflammatory diseases. It can be subdivided into innate responses, class II mediated presentation, class I mediated stimulation of killer cells, and antibody recognition. The responses to gluten proteins and polypeptide regions differs according to the type of gluten sensitivity. The response is also dependent on the genetic makeup of the human leukocyte antigen genes. In gluten sensitive enteropathy, there are four types of recognition, innate immunity, HLA-DQ, and antibody recognition of gliadin and transglutaminase. With idiopathic gluten sensitivity only antibody recognition to gliadin has been resolved. In wheat allergy, the response pathways are mediated through IgE against other wheat proteins and other forms of gliadin.

<span class="mw-page-title-main">Dermatitis herpetiformis</span> Medical condition

Dermatitis herpetiformis (DH) is a chronic autoimmune blistering skin condition, characterised by intensely itchy blisters filled with a watery fluid. DH is a cutaneous manifestation of coeliac disease, although the exact causal mechanism is not known. DH is neither related to nor caused by herpes virus; the name means that it is a skin inflammation having an appearance similar to herpes.

Non-celiac gluten sensitivity (NCGS) or gluten sensitivity is "a clinical entity induced by the ingestion of gluten leading to intestinal and/or extraintestinal symptoms that improve once the gluten-containing foodstuff is removed from the diet, and celiac disease and wheat allergy have been excluded".

The gluten challenge test is a medical test in which gluten-containing foods are consumed and (re-)occurrence of symptoms is observed afterwards to determine whether and how much a person reacts to these foods. The test may be performed in people with suspected gluten-related disorders in very specific occasions and under medical supervision, for example in people who had started a gluten-free diet without performing duodenal biopsy.

Ludvig M. Sollid is a Norwegian physician-scientist whose laboratory has made discoveries in the pathogenesis of HLA associated human disorders, most notably celiac disease. He is currently a Professor of Medicine (immunology) at the University of Oslo and a Senior Consultant at Oslo University Hospital.

References

  1. ↑ Volta U, Cassani F, De Franchis R, et al. (1984). "Antibodies to gliadin in adult coeliac disease and dermatitis herpetiformis". Digestion. 30 (4): 263–70. doi:10.1159/000199118. PMID   6391982.
  2. ↑ Volta U, Lenzi M, Lazzari R, et al. (1985). "Antibodies to gliadin detected by immunofluorescence and a micro-ELISA method: markers of active childhood and adult coeliac disease". Gut. 26 (7): 667–71. doi:10.1136/gut.26.7.667. PMC   1432992 . PMID   3894169.
  3. ↑ Bateman EA, Ferry BL, Hall A, Misbah SA, Anderson R, Kelleher P (2004). "IgA antibodies of coeliac disease patients recognise a dominant T cell epitope of Α-gliadin". Gut. 53 (9): 1274–1278. doi:10.1136/gut.2003.032755. PMC   1774203 . PMID   15306584.
  4. ↑ Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A (1996). "Does cryptic gluten sensitivity play a part in neurological illness?". Lancet. 347 (8998): 369–71. doi:10.1016/S0140-6736(96)90540-1. PMID   8598704. S2CID   37233945.
  5. ↑ Crabbé P, Heremans J (1967). "Selective IgA deficiency with steatorrhea. A new syndrome". Am J Med. 42 (2): 319–26. doi:10.1016/0002-9343(67)90031-9. PMID   4959869.
  6. ↑ Tucker NT, Barghuthy FS, Prihoda TJ, Kumar V, Lerner A, Lebenthal E (1988). "Antigliadin antibodies detected by enzyme-linked immunosorbent assay as a marker of childhood celiac disease". J. Pediatr. 113 (2): 286–9. doi:10.1016/S0022-3476(88)80266-X. PMID   3397791.
  7. ↑ Collin P, Mäki M, Keyriläinen O, Hällström O, Reunala T, Pasternack A (1992). "Selective IgA deficiency and coeliac disease". Scand J Gastroenterol. 27 (5): 367–71. doi:10.3109/00365529209000089. PMID   1529270.
  8. ↑ Matsuo, H.; Morita, E; Tatham, AS; Morimoto, K; Horikawa, T; Osuna, H; Ikezawa, Z; Kaneko, S; Kohno, K; Dekio, S (29 December 2003). "Identification of the IgE-binding Epitope in -5 Gliadin, a Major Allergen in Wheat-dependent Exercise-induced Anaphylaxis". Journal of Biological Chemistry. 279 (13): 12135–12140. doi: 10.1074/jbc.M311340200 . PMID   14699123.
  9. ↑ Denery-Papini S, Lauriére M, Branlard G, et al. (2007). "Influence of the allelic variants encoded at the Gli-B1 locus, responsible for a major allergen of wheat, on IgE reactivity for patients suffering from food allergy to wheat". J. Agric. Food Chem. 55 (3): 799–805. doi:10.1021/jf062749k. PMID   17263477.
  10. ↑ Agardh D (November 2007). "Antibodies against synthetic deamidated gliadin peptides and tissue transglutaminase for the identification of childhood celiac disease". Clin. Gastroenterol. Hepatol. 5 (11): 1276–81. doi:10.1016/j.cgh.2007.05.024. PMID   17683995.
  11. ↑ Antibody Recognition against Native and Selectively Deamidated Gliadin Peptides
  12. ↑ Belén Morón; Ángel Cebolla; Hamid Manyani; Moisés Álvarez-Maqueda; Manuel Megías; María del Carmen Thomas; Manuel Carlos López; Carolina Sousa (2008). "Sensitive detection of cereal fractions that are toxic to celiac disease patients by using monoclonal antibodies to a main immunogenic wheat peptide". American Journal of Clinical Nutrition. 87 (2): 405–414. doi: 10.1093/ajcn/87.2.405 . PMID   18258632.
  13. ↑ Comino, Isabel; Ana Real; Laura de Lorenzo; Hugh Cornell; Miguel Ángel López-Casado; Francisco Barro; Pedro Lorite; Ma Isabel Torres; Ángel Cebolla; Carolina Sousa (12 February 2011). "Diversity in oat potential immunogenicity: basis for the selection of oat varieties with no toxicity in coeliac disease". Gut. 60 (First Online): 915–22. doi:10.1136/gut.2010.225268. PMC   3112367 . PMID   21317420.
  14. ↑ "Draft Revised Standard for Foods for Special Dietary Use for Persons intolerant to Gluten (at Step 8)". page 50-51. Committee on Nutrition and Foods for Special Dietary Uses. JOINT FAO/WHO FOOD STANDARDS PROGRAMME CODEX ALIMENTARIUS COMMISSION. Thirty-first Session Geneva, Switzerland, 30 June – 4 July 2008, Codex Alimentarius Commission REPORT OF THE 29th SESSION OF THE CODEX COMMITTEE ON NUTRITION AND FOODS FOR SPECIAL DIETARY USES
  15. ↑ Hernando A, Mujico JR, Mena MC, Lombardía M, Méndez E (June 2008). "Measurement of wheat gluten and barley hordeins in contaminated oats from Europe, the United States and Canada by Sandwich R5 ELISA". Eur J Gastroenterol Hepatol. 20 (6): 545–54. doi:10.1097/MEG.0b013e3282f46597. PMID   18467914. S2CID   3128946.
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