Biology:Oat sensitivity

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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.[1]

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.[2][3][4][5][6] Oat dust sensitivity in farms found 53% showed reactivity to dust, second only to barley (70%), and almost double that of wheat dust.[7] 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.[8] IgA and IgG responses, meanwhile, like those seen to anti-gliadin antibodies in celiac disease or dermatitis herpetiformis, are not seen in response to avenins in atopic dermatitis patients.[9]

Food allergies to oats can accompany atopy dermatitis.[10] 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 with no histological abnormality, no T-cell reaction to avenin, bearing the rarer DQ2.5trans phenotype, and with anaphylactic reaction to avenin.[11]


Avenin-sensitive enteropathy

Oat toxicity in people with gluten-related disorders depends on the oat cultivar consumed because the immunoreactivities of toxic prolamins are different among oat varieties.[1][12] Furthermore, oats are frequently cross-contaminated with the other gluten-containing cereals.[1] Pure oat (labelled as "pure oat" or "gluten-free oat"[13]) refers to oats uncontaminated with any of the other gluten-containing cereals.[12]

Some cultivars of pure oat could be a safe part of a gluten-free diet, requiring knowledge of the oat variety used in food products for a gluten-free diet.[12] Nevertheless, the long-term effects of pure oats consumption are still unclear[14] and further studies identifying the cultivars used are needed before making final recommendations on their inclusion in the gluten-free diet.[15]

Immunological evidence

Anti-avenin antibodies

In 1992, six proteins were extracted from oats that reacted with a single coeliac sera. Three of the proteins were prolamins, and have been 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 study, three other proteins were identified, one of them an α-amylase inhibitor as identified by protein homology. A follow-up study showed that most celiacs have anti-avenin antibodies (AVAs), with a specificity and sensitivity comparable to anti-gliadin antibodies.[16] A subsequent study found that these AVAs did not result from cross-reaction with wheat.[17] However, recently it has been found that AVAs drop as soon as Triticeae glutens are removed from the diet.[18] Anti-avenin antibodies declined in treated celiacs on an oat diet in 136 individuals, suggesting oats can be involved in celiac disease when wheat is present, but are not involved when wheat is removed from the diet. The study, however, did find an increased number of patients with higher intraepithelial lymphocytes (IELs, 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.[citation needed]

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.[19] 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.[11] 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 four patients had symptoms after oat ingestion, and three had elevated Marsh scores for histology and avenin responsive T-cells, indicating avenin-sensitive enteropathy (ASE). All three patients were the DQ2.5/DQ2 (HLA DR3-DQ2/DR7-DQ2) phenotype. Patients with DQ2.5/DQ2.2 tend to be the most prone toward gluten sensitive enteropathy (GSE), have the highest risk for GS-EATL, and shows signs of more severe disease at diagnosis.[citation needed] While the 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, and 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 of different oat strains to promote various immunochemical aspects of celiac disease. While preliminary, these studies indicate different strains may have different risks for avenin sensitivity.[20][21]

See also

  • Gluten-related disorders
  • List of allergies

References

  1. ↑ 1.0 1.1 1.2 "Gluten-free diet in children: an approach to a nutritionally adequate and balanced diet". Nutrients 5 (11): 4553–65. Nov 18, 2013. doi:10.3390/nu5114553. PMID 24253052. 
  2. ↑ "Oat sensitization in children with atopic dermatitis: prevalence, risks and associated factors". Allergy 62 (11): 1251–6. November 2007. doi:10.1111/j.1398-9995.2007.01527.x. PMID 17919139. 
  3. ↑ "Risk of allergy to food proteins in topical medicinal agents and cosmetics". Eur Ann Allergy Clin Immunol 38 (4): 126–30. April 2006. PMID 16805419. 
  4. ↑ "Allergic contact urticaria to oatmeal". Allergy 57 (12): 1215. December 2002. doi:10.1034/j.1398-9995.2002.23893_7.x. PMID 12464060. 
  5. ↑ "Allergic contact dermatitis due to avena extract". Contact Derm. 42 (6): 364. June 2000. PMID 10871113. 
  6. ↑ "Hypersensitivity to inhaled flour allergens. Comparison between cereals". Allergy 35 (1): 45–56. January 1980. doi:10.1111/j.1398-9995.1980.tb01716.x. PMID 6154431. 
  7. ↑ "Acute symptoms following exposure to grain dust in farming". Environ. Health Perspect. (Brogan &#38) 66: 73–80. April 1986. doi:10.2307/3430216. PMID 3709486. 
  8. ↑ "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. May 1994. doi:10.1111/j.1365-2222.1994.tb00938.x. PMID 8087661. 
  9. ↑ "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. September 1996. doi:10.1159/000237346. PMID 8753845. 
  10. ↑ "Hypereosinophilia, hyper-IgE syndrome, and atopic dermatitis in a toddler with food hypersensitivity". J Investig Allergol Clin Immunol 18 (2): 131–5. 2008. PMID 18447144. 
  11. ↑ 11.0 11.1 "The molecular basis for oat intolerance in patients with celiac disease". PLOS Med. 1 (1): e1. October 2004. doi:10.1371/journal.pmed.0010001. PMID 15526039. 
  12. ↑ 12.0 12.1 12.2 "Role of oats in celiac disease". World J Gastroenterol 21 (41): 11825–31. Nov 7, 2015. doi:10.3748/wjg.v21.i41.11825. PMID 26557006. "It is necessary to consider that oats include many varieties, containing various amino acid sequences and showing different immunoreactivities associated with toxic prolamins. As a result, several studies have shown that the immunogenicity of oats varies depending on the cultivar consumed. Thus, it is essential to thoroughly study the variety of oats used in a food ingredient before including it in a gluten-free diet.". 
  13. ↑ "The gluten-free diet and its current application in coeliac disease and dermatitis herpetiformis.". United European Gastroenterol J 3 (2): 121–35. 2015. doi:10.1177/2050640614559263. PMID 25922672. 
  14. ↑ "Coeliac disease and oats: a systematic review". Postgrad Med J 82 (972): 672–8. Oct 2006. doi:10.1136/pgmj.2006.045443. PMID 17068278. 
  15. ↑ "Pure Oats as Part of the Canadian Gluten-Free Diet in Celiac Disease: The Need to Revisit the Issue.". Can J Gastroenterol Hepatol 2016: 1–8. 2016. doi:10.1155/2016/1576360. PMID 27446824. 
  16. ↑ "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. August 2000. doi:10.1046/j.1365-2362.2000.00684.x. PMID 10964162. 
  17. ↑ "Antibodies to oat prolamines (avenins) in children with coeliac disease". Scand. J. Gastroenterol. 38 (7): 742–6. July 2003. doi:10.1080/00365520310003156. PMID 12889560. 
  18. ↑ "No induction of anti-avenin IgA by oats in adult, diet-treated coeliac disease". Scand. J. Gastroenterol. 43 (2): 161–5. 2008. doi:10.1080/00365520701832822. PMID 18224563. 
  19. ↑ "Avenin fails to induce a Th1 response in coeliac tissue following in vitro culture". Gut 52 (1): 47–52. January 2003. doi:10.1136/gut.52.1.47. PMID 12477758. 
  20. ↑ "Avenins from different cultivars of oats elicit response by coeliac peripheral lymphocytes". Scand. J. Gastroenterol. 42 (11): 1302–5. November 2007. doi:10.1080/00365520701420750. PMID 17852883. 
  21. ↑ "In vitro tests indicate that certain varieties of oats may be harmful to patients with coeliac disease". J. Gastroenterol. Hepatol. 22 (4): 528–31. April 2007. doi:10.1111/j.1440-1746.2006.04512.x. PMID 17376046. 



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