Avenins

Limitations identified within the scientific database include limited data on long-term consumption, limited numbers of participants in challenge studies, and limited reporting about the reasons for withdrawals from study protocols. Furthermore, some evidence suggests that a small number of individuals with celiac disease may be intolerant to pure oats and some evidence from in vitro studies suggests that an immunological response to oat avenins can occur in the absence of clinical manifestations of celiac disease as well as suggesting that oat cultivars vary in toxicity. 

Arentz-Hansen et al. (2004) ( continuation of Lundin et al, 2003) 9 CD subjects who had history of oats exposure ( 5/9 from same study population) Derivation of polyclonal T cell lines In vitro duodenal mucosal cultures were challenged with either pepsin or Avenin-reactive T cell lines recognized avenin peptides in the context of HLA-DQ2 A substantial proportion of the avenin-reactive T cell appears to be specific to avenin Some CD patients have avenin-reactive mucosal T cells that can cause mucosal inflammation... 

In Vitro—other Silano et al. (2007) 10 children with verified CD Peripheral lymphocyte samples exposed to avenins from 4 different oat varieties Lampton, Astra, Ava, and Nave Lymphocyte proliferation and IFN-y release in the culture medium were measured as indexes on immune activation All varieties of oats were immunogenic, with Lampton and Ava avenins inducing lymphocyte activation similar to gliadin Astra and Nave avenins showed less immunogenicity More evidence is needed to show the safety of oats and varieties of low toxicity... 

Silano et al. (2007) N/A 3 varieties of oats were tested by 2 assays based on the known ability of PT digests of celiac-active Avenins from Italian variety Astra and the Australia variety Mortlook were more active than the Results indicate that some varieties of oats may be potentially harmful... 

Serology Guttormsen et al. 136 CD subjects Serum samples were Gliadin, avenin, and tTG Findings support the... 

CD subjects oats (24 g/day (mean) 6 months minimum) and 54 CD subjects GFD without oats Control 139 non-CD subjects IgA to wheat gliadin, oats avenin, and tTG CD subjects adult CD patients can tolerate oats Ingestion of oats does not cause increased levels of IgA against oats in CD patients on GFD... 

In addition to the pivotal studies, several publications (Table 6.2) used other methods to test the response of individuals with celiac disease who were introduced to oats. These studies did not fulfill the selection criteria of pivotal studies namely an in vivo oats challenge with an intestinal/skin biopsy to assess the biological response to the introduction of oats into an otherwise gluten-free diet. Instead, they used various in vitro techniques to assess the immune response to avenin, or serology without an intestinal mucosal biopsy. Most of the methods used duodenal mucosal cultures prepared from biopsies or intestinal T cell lines obtained from individuals with celiac disease. Other studies measured the immunogenic reaction in peripheral lymphocytes or measured the presence of various antibodies in individuals with verified celiac disease who included oats in their diet, in comparison with a reference group (Table 6.2). Some of these studies used patients that were previously included in pivotal studies. These studies are identified with an asterisk ( ) in Table 6.2. 

In contrast, other in vitro studies (Kilmartin et al., 2003, 2006) report that purified avenin from oats is not immunogenic to the intestinal mucosa of patients with celiac disease. 

From currently available data, one adult patient (1/170) challenged with oats was reported to have a severe adverse reaction to oats. Approximately 6% of adults and 9% of children withdrew from clinical trials due to reported adverse effects from the inclusion of oats in their diet. This evidence, along with the indication from some in vitro studies of an immunological response to avenin in the absence of clinical manifestations of celiac disease and the limitations of the database (previously discussed), supports a cautionary approach for the introduction of oats into a gluten-free diet until the prevalence of oats intolerance among people with celiac disease is well established (Dickey, 2008 Garsed and Scott, 2007). 

Wheat, rye, and barley have a common ancestral origin in the grass family. Oats are more distantly related to the analogous proteins in wheat, rye, and barley and the oat prolamins (avenin) have substantially lower proline content. Avenin accounts for 5-15% of the total protein in oats, whereas in wheat, barley, and rye, prolamins constitute 40-50% of the total protein (Kilmartin et al., 2006). Some investigators believe that there are similarities between the protein structure of oats and some wheat-like sequences, which may indicate that large amounts of oats could potentially be toxic to patients with celiac disease. However, the putative toxic amino acid sequences are less frequent in avenin than in other prolamins, which explains the less toxic nature of oats (Arentz-Hansen et al., 2004 Ellis and Ciclitira, 2001, 2008 Shan et al., 2005 Vader et al., 2002, 2003). 

Guttormsen, V., Lovik, A., Bye, A., Bratlie, J., Morkrid, L., and Lundin, K. E. (2008). No induction of anti-avenin IgA by oats in adult, diet-treated coeliac disease. Scand. J. Gastroenterol. 43,161-165. 

Kilmartin, C., Lynch, S., Abuzakouk, M., Wieser, H., and Feighery, C. (2003). Avenin fails to induce a Thl response in coeliac tissue following in vitro culture. Gut 52, 47-52. 

Silano, M., Di Benedetto, R., Maialetti, F., De Vincenzi, A., Calcaterra, R., Cornell, H. J., and De Vincenzi, M. (2007b). Avenins from different cultivars of oats elicit response by coeliac peripheral lymphocytes. Scand. J. Gastroenterol. 42,1302-1305. 

E. Abderhalden UND Y. HXmalainen. Die Monoamitiosduren des Avenins, Zeit. physiol. Chem., 1907, 52, 515-320. 

Gliadins are prolamins, a group of plant storage proteins with a high proline content, found in the seeds of cereal grains wheat (gliadin), barley (hordein), rye (secalin), corn (zein) and, as a minor protein, avenin in oats. 

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