



Normal long villi (above) and Coeliac disease blunted villi (below).





Coeliac disease is an autoimmune disease in which a dysfunctional immune response occurs in response to gluten consumption to specific epitopes found in gluten.





In Coeliac’s patients, when Gluten is consumed, a component of gluten called gliadin is absorbed across the villi and then it is presented by HLA molecules on antigen-presenting cells to T cells. The binding of the antigen-presenting cells and T cells containing the gliadin peptide subsequently causes an inflammatory response, whereby the intestinal mucosa is targeted and damaged leading to bloating, diarrhoea, and malabsorption.





The presence of HLA-DQ2 or -DQ8 allows gliadin to be presented as an immunogenic epitope, therefore, there is some genetic predisposition to this disease as 95% of individuals have HLA DQ2 and 5% have HLA DQ8, however not all with these HLA types go on to develop coeliacs, therefore, there is a combination of environmental and genetic factors that cause the disease.





Unfortunately, the treatment options for individuals with Coeliacs are limited to a gluten-free diet, however, their diet may not be completely gluten-free as gluten is widespread and there could be trace amounts of gluten in their food.





A research article was published in BMC Plant Biology , the research laid a foundation for the development of CRISPR edited Gluten which could limit immunogenicity of gluten one day and be consumed by Coeliac patients.





In this study, the scientists determined the genetic diversity of gamma and alpha gliadin gene sequences in bread wheat cultivar Fielder, this information was used to create six sgRNA that targeted immunogenic epitopes that potentially trigger Coeliacs disease, including alpha gliadin, gamma gliadin or both.

After the gene editing, the gliadin profiles of the CRISPR edited gliadin were compared to the non-edited gliadin. In several cases, the protein signature for the CRISPR edited gliadin was different and therefore CRISPR was able to successfully modify the epitopes.

Therefore, in the future, the immunogenicity of gluten could be limited by complete deletion or mutation of the immunogenic epitopes in gluten with CRISPR gene editing. This would require a lot of refinement as the wheat lines would need to be producing homozygous mutations and be extensively analysed with immunological testing to determine the immunogenicity of the CRISPR edited wheat lines to ensure safe/tolerable consumption by Coeliac patients.





Reference:

https://bmcplantbiol.biomedcentral.com/articles/10.1186/s12870-019-1889-5