Oat sensitivity

Oat sensitivity represents a sensitivity to the proteins found in oats, Avena sativa. Sensitivity to oats as a result of allergy or to the seed storage proteins either inhaled or ingested. A more complex condition results to individuals who have gluten-sensitive enteropathy in which there is also a response to avenin, the glutinous protein in oats similar to the gluten within wheat.

Oat allergy

Studies on farmers with grain dust allergy and children with atopy dermatitis reveal that oat proteins can act as both respiratory and skin allergens.^{[1][2][3][4][5]} Oat-dust sensitivity in farms found 53% showed reactivity to dust second only to barley (70%) and almost double that of wheat dust.^[6] The 66 kDa protein in oats was visualized by 28 out of 33 sera (84%), however, there was evident non-specific binding to this region and thus it may also represent lectin-like binding.^[7] However, IgA and IgG responses, like those seen to anti-gliadin antibodies in celiac disase or dermatitis herpetiformis, are not seen to avenins in atopic dermatitis patients.^[8] Food allergies to oats can accompany atopy dermatitis.^[9] Oat avenins share similarities with γ and ω-gliadins of wheat, based on these similarities they could potentiate both enteropathic response and anaphylactic responses. Oat allergy in gluten-sensitive enteropathy can explain an avenin sensitive individual who no histological abnormality, no T-cell reaction to avenin, bore the rarer DQ2.5trans phenotype and had anaphylactic reaction to avenin.^[10]

Further information: Wheat allergy

and Wheat dependent exercise-induced anaphylaxis

Avenin-sensitive enteropathy

Gluten-sensitive enteropathy and its common and more severe form, coeliac disease, results in the increased inflammation of the tissues of the small bowel eventually leading to villus atrophy. The disease progresses from increase lymphocyte counts to eventual flattening of the villi and crypt hyperplasia. Originally, oats were believed to cause coeliac disease. However this confusion was largely due to significant contamination of oats with wheat, barley or rye. A recent review of controlled oat tolerance studies indicated only one documented avenin-sensitive enteropathy (ASE) in 165, placing the risk of ASE at 0.6% of coeliac disease population. However, during the controlled studies, 17 candidates dropped out due to symptoms after ingestion of GF oats and were not tested at the completion of their respective studies. As a result, the actual risk of ASE in the coelic disease population may be slightly higher.^[11]

Further information: The oat controversy in gluten sensitivity

Immunological evidence

Anti-avenin antibodies

In 1992, 6 protein were extracted from oats that reacted with a single coeliac sera. The proteins, prolamins, were called CIP 1 (gamma avenin), CIP 2, and CIP3. They had the following amino-acid sequences:

Antibody recognition sites on three avenins
CIP1 (γ-avenin)               P S E Q Y Q P Y P E Q Q Q P F 
CIP2 (γ-avenin) T T T V Q Y D P S E Q Y Q P Y P E Q Q Q P F V Q Q Q P P F 
CIP3 (α-avenin) T T T V Q Y N P S E Q Y Q P Y  

within the same paper 3 other proteins were identified, one was an α-amylase inhibitor, identified by protein homology. A follow-up study showed that most celiacs have anti-avenin antibodies(AVA), with a specificity and sensitivity comparable to anti-gliadin antibodies.^[12] A subsequent study found that these AVA did not result from cross-reaction with wheat.^[13] However recently it has been found that AVA drop as soon as Triticeae glutens are removed from the diet.^[14] Anti-avenin antibodies decline in treated celiacs on an oat diet in 136 individuals this suggests that oats can be involved in celiac disease when wheat is present, but is not involved when wheat is removed from the diet. The study however did find an increase number of patients with higher intraepithelial lymphocytes (IEL, a type of white bloodcell) in the oat-eating cohort. Regardless of whether or not this observation is a direct allergic immune response, by itself this is essentially benign.

Cellular immunity

In gluten-sensitive enteropathy, prolamins mediate between T-cells and antigen presenting cells, whereas anti-transglutaminase antibodies confer autoimmunity via covalent attachment to gliadin. In 16 examined coeliacs, none produced a significant Th1 response.^[15] Th1 responses are needed to stimulate T-helper cells that mediate disease. This could indicate that coeliac disease does not directly involve avenin or that the sample size was too small to detect the occasional responder.

Evidence that there are exceptional cases came in a 2004 study on oats.^[10] The patients drafted for this study were those who had symptoms of celiac disease when on a 'pure-oat' challenge, therefore not representative of a celiac sample. This study found that 4 patients had symptoms after oat ingestion, 3 had elevated Marsh scores for histology, and avenin responsive T-cells, indicating avenin-sensitive enteropathy(ASE). All three patients were DQ2.5/DQ2 (HLA DR3-DQ2/DR7-DQ2) phenotype. Patients with DQ2.5/DQ2.2 tend to be the most prone toward GSE, have the highest risk for GS-EATL, and shows signs of more severe disease at diagnosis.^{[citation needed]} While DQ2.5/DQ2 phenotype represents only 25% of celiac patients, it accounts for all of the ASE celiacs, and 60-70% of patients with GS-EATL.^{[citation needed]} Synthetic avenin peptides were synthesized either in native or deamidated form, the deamidated peptides showed higher response.

DQ2.5/T-cell receptor recognition from 2 Oat-sensitive coeliacs
TCR-Site1                             Y Q P Y P E Q E~E~P F V
TCR-Site2                           Q Y Q P Y P E Q Q Q P F V Q Q Q Q
Antibody recognition site(see above)
CIP2 (γ-avenin) T T T V Q Y D P S E Q Y Q P Y P E Q Q Q P F V Q Q Q P P F 

The overlap of the antibody and T-cell sites, given trypsin digestion of avenin, suggest this region is dominant in immunity. The TCR-site1 was synthetically made as deamidated ("~E~") and native peptide requires transglutaminase to reach full activation. Two studies to date have looked at the ability for different oat-strains to promote various immunochemical aspects of celiac disease. While preliminary these studies indicate different strains may have different risk for avenin-sensitivity^[16][17]

Oats and coeliac disease

There is a great deal of conflicting information regarding the inclusion of oats within a gluten-free diet. Although cross-contamination in the field and during processing partially explains the different reactions that celiacs can have to oat, a recent study indicates that there are also different amounts of gluten present in different cultivars of oat. The G12 antibody, used in the study, is currently the only one that can reliably distinguish between varieties of oat.^[18] Previous studies have indicated both children and adult coeliacs are largely tolerant of oats.^{[19][20][21][22]} Other studies have followed both children and adults for 1, 2 and 5 years on the 'uncontaminated'-oat^[23] containing gluten-free diet.^{[24][25][26][27][28]} These studies failed to show significant changes in intestinal morphology indication a relapse of celiac disease. Anti-gliadin and reticulin antibodies as well as numbers of intraepithelial lymphocytes (IELs) did not differ significantly between oat-eating celiacs and non-oat eating controls in remission.^[29] Invitro tests that are sensitive to wheat gluten found that tryptic peptides of avenin could not induce EMA production in supernatant fluid from cultured duodenal mucosa specimen from celiac patients.^[30] Algorithms that successfully predict T cell stimulatory peptides in gluten identified many similar peptides in hordeins and secalins but not in oat avenins.^[31] The Canadian Celiac Association suggests that adults can consume up to 70g of oats and children up to 25g per day,^[32] however, two studies indicated that adults could consume 93 grams (3.3 ounces) of oats per day. There is no evidence that oats can trigger GSE, only that in a small number of celiacs disease can be sustained or reinitiated by oats once triggered by wheat. A recent paper examining the IEL of celiac patients in remission showed a significantly higher number of IEL in oat-eating celiacs, in addition antibodies to avenin remain low as long as the diet is gluten-free but higher anti-avenin antibodies can increase with a diet containing wheat.^{[citation needed]}

Further information: The oat controversy in gluten sensitivity

Some coeliacs respond adversely to oats. Estimates range from 0.5 to 20% of the GSE population. With coeliac disease non-compliance to achieve normal intestinal morphology is a risk factor for refractory disease and cancer.^{[citation needed]}

Further information: Cancers and Refractory disease associated with gluten-sensitivity

See also

• List of allergies

References

1. ^ Boussault P, Léauté-Labrèze C, Saubusse E, et al. (November 2007). "Oat sensitization in children with atopic dermatitis: prevalence, risks and associated factors". Allergy 62 (11): 1251–6. doi:10.1111/j.1398-9995.2007.01527.x. PMID 17919139. 
2. ^ Codreanu F, Morisset M, Cordebar V, Kanny G, Moneret-Vautrin DA (April 2006). "Risk of allergy to food proteins in topical medicinal agents and cosmetics". Eur Ann Allergy Clin Immunol 38 (4): 126–30. PMID 16805419. 
3. ^ De Paz Arranz S, Pérez Montero A, Remón LZ, Molero MI (December 2002). "Allergic contact urticaria to oatmeal". Allergy 57 (12): 1215. doi:10.1034/j.1398-9995.2002.23893_7.x. PMID 12464060. 
4. ^ Pazzaglia M, Jorizzo M, Parente G, Tosti A (June 2000). "Allergic contact dermatitis due to avena extract". Contact Derm. 42 (6): 364. PMID 10871113. 
5. ^ Baldo BA, Krilis S, Wrigley CW (January 1980). "Hypersensitivity to inhaled flour allergens. Comparison between cereals". Allergy 35 (1): 45–56. doi:10.1111/j.1398-9995.1980.tb01716.x. PMID 6154431. 
6. ^ Manfreda J, Holford-Strevens V, Cheang M, Warren CP (April 1986). "Acute symptoms following exposure to grain dust in farming". Environ. Health Perspect. (Brogan &#38) 66: 73–80. doi:10.2307/3430216. JSTOR 3430216. PMC 1474397. PMID 3709486. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1474397. 
7. ^ Varjonen E, Savolainen J, Mattila L, Kalimo K (May 1994). "IgE-binding components of wheat, rye, barley and oats recognized by immunoblotting analysis with sera from adult atopic dermatitis patients". Clin. Exp. Allergy 24 (5): 481–9. doi:10.1111/j.1365-2222.1994.tb00938.x. PMID 8087661. 
8. ^ Varjonen E, Kalimo K, Savolainen J, Vainio E (September 1996). "IgA and IgG binding components of wheat, rye, barley and oats recognized by immunoblotting analysis with sera from adult atopic dermatitis patients". Int. Arch. Allergy Immunol. 111 (1): 55–63. doi:10.1159/000237346. PMID 8753845. 
9. ^ Estrada-Reyes E, Hernnández-Román MP, Gamboa-Marrufo JD, Valencia-Herrera A, Nava-Ocampo AA (2008). "Hypereosinophilia, hyper-IgE syndrome, and atopic dermatitis in a toddler with food hypersensitivity". J Investig Allergol Clin Immunol 18 (2): 131–5. PMID 18447144. 
10. ^ ^{a b} Arentz-Hansen H, Fleckenstein B, Molberg Ø, et al. (October 2004). "The molecular basis for oat intolerance in patients with celiac disease". PLoS Med. 1 (1): e1. doi:10.1371/journal.pmed.0010001. PMC 523824. PMID 15526039. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=523824. 
11. ^ Garsed K, Scott BB (February 2007). "Can oats be taken in a gluten-free diet? A systematic review". Scand. J. Gastroenterol. 42 (2): 171–8. doi:10.1080/00365520600863944. PMID 17327936. 
12. ^ Ribes-Koninckx C, Alfonso P, Ortigosa L, et al. (August 2000). "A beta-turn rich oats peptide as an antigen in an ELISA method for the screening of coeliac disease in a paediatric population". Eur. J. Clin. Invest. 30 (8): 702–8. doi:10.1046/j.1365-2362.2000.00684.x. PMID 10964162. http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0014-2972&date=2000&volume=30&issue=8&spage=702. 
13. ^ Hollén E, Högberg L, Stenhammar L, Fälth-Magnusson K, Magnusson KE (July 2003). "Antibodies to oat prolamines (avenins) in children with coeliac disease". Scand. J. Gastroenterol. 38 (7): 742–6. doi:10.1080/00365520310003156. PMID 12889560. 
14. ^ Guttormsen V, Løvik A, Bye A, Bratlie J, Mørkrid L, Lundin KE (2008). "No induction of anti-avenin IgA by oats in adult, diet-treated coeliac disease". Scand. J. Gastroenterol. 43 (2): 161–5. doi:10.1080/00365520701832822. PMID 18224563. 
15. ^ Kilmartin C, Lynch S, Abuzakouk M, Wieser H, Feighery C (January 2003). "Avenin fails to induce a Th1 response in coeliac tissue following in vitro culture". Gut 52 (1): 47–52. doi:10.1136/gut.52.1.47. PMC 1773501. PMID 12477758. http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=12477758. 
16. ^ Silano M, Di Benedetto R, Maialetti F, et al. (November 2007). "Avenins from different cultivars of oats elicit response by coeliac peripheral lymphocytes". Scand. J. Gastroenterol. 42 (11): 1302–5. doi:10.1080/00365520701420750. PMID 17852883. 
17. ^ Silano M, Dessì M, De Vincenzi M, Cornell H (April 2007). "In vitro tests indicate that certain varieties of oats may be harmful to patients with coeliac disease". J. Gastroenterol. Hepatol. 22 (4): 528–31. doi:10.1111/j.1440-1746.2006.04512.x. PMID 17376046. 
18. ^ 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). "Diversity in oat potential immunogenicity: basis for the selection of oat varieties with no toxicity in coeliac disease". Gut Gut Online First. http://gut.bmj.com/content/early/2011/02/11/gut.2010.225268.abstract. Retrieved 12 March 2011. 
19. ^ Dissanayake AS, Truelove SC, Whitehead R (October 1974). "Lack of harmful effect of oats on small-intestinal mucosa in coeliac disease". Br Med J 4 (5938): 189–91. doi:10.1136/bmj.4.5938.189. PMC 1612349. PMID 4417208. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1612349. 
20. ^ Janatuinen EK, Pikkarainen PH, Kemppainen TA, et al. (October 1995). "A comparison of diets with and without oats in adults with celiac disease". N. Engl. J. Med. 333 (16): 1033–7. doi:10.1056/NEJM199510193331602. PMID 7675045. http://content.nejm.org/cgi/pmidlookup?view=short&pmid=7675045&promo=ONFLNS19. 
21. ^ Srinivasan U, Leonard N, Jones E, et al. (November 1996). "Absence of oats toxicity in adult coeliac disease". BMJ 313 (7068): 1300–1. PMC 2352731. PMID 8942690. http://bmj.com/cgi/pmidlookup?view=long&pmid=8942690. 
22. ^ Hoffenberg EJ, Haas J, Drescher A, et al. (September 2000). "A trial of oats in children with newly diagnosed celiac disease". J. Pediatr. 137 (3): 361–6. doi:10.1067/mpd.2000.109003. PMID 10969261. 
23. ^ Dor R, Shanahan DJ (November 2002). "Oats and coeliac disease". Gut 51 (5): 757; author reply 757–8. doi:10.1136/gut.51.5.757. PMC 1773434. PMID 12377824. http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=12377824. "patients used oat products from major Finnish mills. These products have been found to be free of contamination" 
24. ^ Janatuinen EK, Kemppainen TA, Julkunen RJ, et al. (March 2002). "No harm from five year ingestion of oats in coeliac disease". Gut 50 (3): 332–5. doi:10.1136/gut.50.3.332. PMC 1773136. PMID 11839710. http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=11839710. 
25. ^ Dor R, Shanahan DJ (November 2002). "Oats and coeliac disease". Gut 51 (5): 757; author reply 757–8. doi:10.1136/gut.51.5.757. PMC 1773434. PMID 12377824. http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=12377824. 
26. ^ Størsrud S, Olsson M, Arvidsson Lenner R, Nilsson LA, Nilsson O, Kilander A (January 2003). "Adult coeliac patients do tolerate large amounts of oats". Eur J Clin Nutr 57 (1): 163–9. doi:10.1038/sj.ejcn.1601525. PMID 12548312. 
27. ^ Högberg L, Laurin P, Fälth-Magnusson K, et al. (May 2004). "Oats to children with newly diagnosed coeliac disease: a randomised double blind study". Gut 53 (5): 649–54. doi:10.1136/gut.2003.026948. PMC 1774046. PMID 15082581. http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=15082581. 
28. ^ Holm K, Mäki M, Vuolteenaho N, et al. (May 2006). "Oats in the treatment of childhood coeliac disease: a 2-year controlled trial and a long-term clinical follow-up study". Aliment. Pharmacol. Ther. 23 (10): 1463–72. doi:10.1111/j.1365-2036.2006.02908.x. PMID 16669961. 
29. ^ Janatuinen EK, Kemppainen TA, Pikkarainen PH, et al. (March 2000). "Lack of cellular and humoral immunological responses to oats in adults with coeliac disease". Gut 46 (3): 327–31. doi:10.1136/gut.46.3.327. PMC 1727854. PMID 10673292. http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=10673292. 
30. ^ Picarelli A, Di Tola M, Sabbatella L, et al. (July 2001). "Immunologic evidence of no harmful effect of oats in celiac disease". Am. J. Clin. Nutr. 74 (1): 137–40. PMID 11451729. http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=11451729. 
31. ^ Vader LW, de Ru A, van der Wal Y, et al. (March 2002). "Specificity of tissue transglutaminase explains cereal toxicity in celiac disease". J. Exp. Med. 195 (5): 643–9. doi:10.1084/jem.20012028. PMC 2193762. PMID 11877487. http://www.jem.org/cgi/pmidlookup?view=long&pmid=11877487. 
32. ^ Rashid M, Butzner D, Burrows V, et al. (October 2007). "Consumption of pure oats by individuals with celiac disease: a position statement by the Canadian Celiac Association". Can. J. Gastroenterol. 21 (10): 649–51. PMC 2658132. PMID 17948135. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2658132.