Oat sensitivity

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 also a 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

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 increased 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 the coeliac disease population. However, during the controlled studies, 17 candidates dropped out due to symptoms after ingestion of gluten-free 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.^[12]

Immunological evidence

Anti-avenin antibodies

In 1992, six proteins 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 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.^[13] A subsequent study found that these AVAs did not result from cross-reaction with wheat.^[14] However, recently it has been found that AVAs drop as soon as Triticeae glutens are removed from the diet.^[15] 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.

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.^[16] 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. 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. 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.^[17][18]

Oats and celiac disease

There is a great deal of conflicting information regarding the inclusion of oats in a gluten-free diet. Although cross-contamination in the field and during processing partially explains the different reactions that celiacs can have to oats, a recent study indicates that there are also different amounts of avenin 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.^[19] Previous studies have indicated both children and adult coeliacs are largely tolerant of oats.^{[20][21][22][23]} Other studies have followed both children and adults for one, two, and five years on the "uncontaminated" oat^[24] containing gluten-free diet.^{[25][26][27][28][29]} These studies failed to show significant changes in intestinal morphology indicative of 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.^[30] 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.^[31] Algorithms that successfully predict T cell stimulatory peptides in gluten identified many similar peptides in hordeins and secalins, but not in oat avenins.^[32] The Canadian Celiac Association suggests that adults can consume up to 70g of oats per day, and children up to 25g.^[33] However, two studies indicated that celiac 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 levels of celiac patients in remission showed a significantly higher number of IELs 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.

Some coeliacs respond adversely to oats. Estimates range from 0.5 to 20% of the GSE population. With coeliac disease, non-compliance in attempting to achieve normal intestinal morphology is a risk factor for refractory disease and cancer.

See also

• List of allergies

References