Anti-gliadin antibodies

AbBox
Antigen = glaidin
SharedInfo = Yes
SI_Source = "Triticum aestivum"
SI_Gene =
SI_Organ =
SI_Tissue =
SI_Cell =
SI_Also =
SI_Disease =
SI_Class =
SI_IgGSubclass =
SI_HLA1 =
SI_HLA2 =
SI_HLA3 =
SI_AssociatedGene =
SI_TCellRestrict =
Isoform1 = α/β-gliadin
I1_Source =
I1_Gene = Gli-X2
I1_Organ = Intestine (Small)
I1_Tissue =
I1_Cell =
I1_Also = Epithelial extracellular matrix
I1_Disease = Coeliac disease
I1_Class = IgA, IgG
I1_IgGSubclass =
I1_HLA1 = DQ2.5
I1_HLA2 = DQ8
I1_HLA3 = DQ2.2/DQ7.5
I1_AssociatedGene =
I1_TCellRestrict = DQ2, DQ8
Isoform2 = γ-gliadin
I2_Source =
I2_Gene = Gli-X3
I2_Organ = (See α/β-gliadin)
I2_Disease = Coeliac disease
I2_Class = IgA, IgG
I2_IgGSubclass =
I2_HLA1 = DQ2.5
I2_HLA2 = DQ8
I2_HLA3 = DQ2.2/DQ7.5
I2_AssociatedGene =
I1_TCellRestrict = DQ2, DQ8
Isoform3 = ω-gliadin
I3_Source = & "Aegilops speltoides"
I3_Gene = Gli-B1
I3_Organ = Vascular, Respiratory
I3_Tissue = Serum, Dermis
I3_Cell = Mast Cells, Eosinophils
I3_Also =
I3_Disease = EIA, Baker's Allergy
I3_Class = IgE
I3_IgGSubclass =
I3_HLA1 =
I3_HLA2 =
I3_HLA3 =
I3_AssociatedGene =

Anti-gliadin antibodies are produced in response to gliadin, a prolamin found in the wheat. In bread wheat it is encoded by three different genomes, AA, BB, and DD. These genomes can produce slight 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 across with certain species in those taxa, or over many taxonomically defined grass tribes.

Anti-gliadin IgA

This antibody is found in ~80% of patients with coeliac disease.cite journal | author = Volta U, Cassani F, De Franchis R, "et al" | title = Antibodies to gliadin in adult coeliac disease and dermatitis herpetiformis | journal = Digestion | volume = 30 | issue = 4 | pages = 263–70 | year = 1984 | pmid = 6391982 | doi = ] cite journal | author = Volta U, Lenzi M, Lazzari R, "et al" | title = Antibodies to gliadin detected by immunofluorescence and a micro-ELISA method: markers of active childhood and adult coeliac disease | journal = Gut | volume = 26 | issue = 7 | pages = 667–71 | year = 1985 | pmid = 3894169 | doi = ] It is directedagainst the alpha/beta and gamma (α,β,γ) gliadins.cite journal | author = Bateman EA, Ferry BL, Hall A, Misbah SA, Anderson R, and Kelleher P. | title = IgA antibodies of coeliac disease patients recognise a dominant T cell epitope of A-gliadin. | journal = Gut. | volume = 53 | issue = 9 | pages = 1274–1278 | year = 2004 | pmid = 15306584 | doi = 10.1136/gut.2003.032755] It is also found in a number of patients who are not enteropathic. Some of these patients may have neuropathies that respond favorably to gluten elimination diet. This is referred to as gluten-sensitive idiopathic neuropathy.cite journal | author = Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A | title = Does cryptic gluten sensitivity play a part in neurological illness? | journal = Lancet | volume = 347 | issue = 8998 | pages = 369–71 | year = 1996 | pmid = 8598704 | doi = ] Clinically these antibodies and IgG antibodies to gliadin are abbreviated as AGA.

Anti-gliadin IgG

IgG antibodies 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 idiopathic gluten sensitivity. [cite journal | author = Crabbé P, Heremans J | title = Selective IgA deficiency with steatorrhea. A new syndrome | journal = Am J Med | volume = 42 | issue = 2 | pages = 319–26 | year = 1967 | pmid = 4959869 | doi = 10.1016/0002-9343(67)90031-9] cite journal | author = Tucker NT, Barghuthy FS, Prihoda TJ, Kumar V, Lerner A, Lebenthal E | title = Antigliadin antibodies detected by enzyme-linked immunosorbent assay as a marker of childhood celiac disease | journal = J. Pediatr. | volume = 113 | issue = 2 | pages = 286–9 | year = 1988 | pmid = 3397791 | doi = ] [cite journal | author = Collin P, Mäki M, Keyriläinen O, Hällström O, Reunala T, Pasternack A | title = Selective IgA deficiency and coeliac disease | journal = Scand J Gastroenterol | volume = 27 | issue = 5 | pages = 367–71 | year = 1992|pmid = 1529270 | doi = 10.3109/00365529209000089] and IgA-less is associated with Coeliac disease.Anti-gliadin antibodies are frequently found with anti-transglutaminase antibodies

Anti-gliadin IgE

The IgE antibodies are more typically found in allergy-related conditions suchas urticaria, asthma, and wheat-dependent exercise-induced anaphylaxis. The target of the most allergenic antibodies are ω-5 gliadin,cite journal | author = Matsuo H, Morita E, Tatham AS, Morimoto K, Horikawa T, Osuna H, Ikezawa Z, Kaneko S, Kohno K, and Dekio S. | title = Identification of the IgE-binding epitope in omega-5 gliadin, a major allergen in wheat-dependent exercise-induced anaphylaxis. | journal = J Biol Chem. | volume = 279 | issue = 13 | pages = 12135–12140 | year = 2004 | pmid = 14699123 | doi = 10.1074/jbc.M311340200] that is encoded by the Gli-1B gene found on the B haplome ("Aegilops speltoides" derived) of wheat.cite journal | author = Denery-Papini S, Lauriére M, Branlard G, "et al" | title = 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 | journal = J. Agric. Food Chem. | volume = 55 | issue = 3 | pages = 799–805 | year = 2007 | pmid = 17263477 | doi = 10.1021/jf062749k]

Anti-gliadin antibodies and the gluten-free diet

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 test measure the level of AGA relative to a standard, such as a level of 10 = point in 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 highAGA values may take 2 years to return to the normal range.

Refractory coeliac diease (RCD). RCD or non-strict gluten-free diet can be two cause of failure of AGA to return to normality on the GF diet. 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.cite journal |author=Agardh D |title=Antibodies against synthetic deamidated gliadin peptides and tissue transglutaminase for the identification of childhood celiac disease |journal=Clin. Gastroenterol. Hepatol. |volume=5 |issue=11 |pages=1276–81 |year=2007 |month=November |pmid=17683995 |doi=10.1016/j.cgh.2007.05.024 |url=] [ [http://www.clinchem.org/cgi/content/full/47/11/2023 Antibody Recognition against Native and Selectively Deamidated Gliadin Peptides] ]

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 hybridoma that produces monoclonal antibodies (Mab). 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, or they can detect antigens over broad taxa. The R5 sandwich assay is one such assay. This assay can recognize wheat, barley and rye which makes it ideal for evaluating the presence of contaminants in gluten-free foods. This antibody is a recommended testing protocol in a proposed revision of the Codex Alimentarius.

The new standards, in part, came about because of new sensitive and specific testing procedures."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 [http://www.codexalimentarius.net/download/report/687/al08_26e.pdf REPORT OF THE 29th SESSION OF THE CODEX COMMITTEE ON NUTRITION AND FOODS FOR SPECIAL DIETARY USES ] ] 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.cite journal |author=Hernando A, Mujico JR, Mena MC, Lombardía M, Méndez E |title=Measurement of wheat gluten and barley hordeins in contaminated oats from Europe, the United States and Canada by Sandwich R5 ELISA |journal=Eur J Gastroenterol Hepatol |volume=20 |issue=6 |pages=545–54 |year=2008 |month=June |pmid=18467914 |doi=10.1097/MEG.0b013e3282f46597 |url=] Another monoclonal antibody that targets the pathogenic "33mer" of α-gliadin shows a low level of crossreactivity with oats, though contamination may be an issue in this study.cite journal |author=Morón B, Bethune MT, Comino I, "et al" |title=Toward the assessment of food toxicity for celiac patients: characterization of monoclonal antibodies to a main immunogenic gluten peptide |journal=PLoS ONE |volume=3 |issue=5 |pages=e2294 |year=2008 |pmid=18509534 |pmc=2386552 |doi=10.1371/journal.pone.0002294 |url=] [Móron et al. do not state a source of oat or purity] These kits are capable of detecting and discriminating sources of contamination of oats, and can be supplimented with genetic tests, such a species specific PCR.

References