Targeted modification of wheat grain protein to reduce the content of celiac causing epitopes

Abstract

The prolamin peptides in wheat gluten and in the homologous storage proteins of barley and rye cause painful chronic erasure of microvilli of the small intestine epithelium in celiac patients. If untreated, it can lead to chronic diarrhea, abdominal distension, osteoporosis, weight-loss due to malabsorption of nutrients, and anemia. In addition to congenital cases, life-long exposure to gluten proteins in bread and pasta can also induce development of celiac sprue in adults. To date, the only effective treatment is life-long strict abstinence from the staple food grains. Complete exclusion of dietary gluten is, however, difficult due to use of wheat in many foods, incomplete labeling and social constraints. Thus, finding alternative therapies for this most common foodborne disease remained an active area of research, which has led to many suggestions in last few years. The pros and cons associated with these therapies were reviewed in the present communication. As different celiac patients are immunogenic to different members of the undigestible proline/glutamine rich peptides of ~149 gliadins and low molecular weight glutenin subunits as well as the six high molecular weight glutenin subunits, an exhaustive digestion of the immunogenic peptides in the stomach, duodenum, jejunum, and ileum of celiacs is required. In view of the above, we evaluated the capacity of cereal grains to synthesize and store the enzymes prolyl endopeptidase from Flavobacterium meningosepticum and the barley cysteine endoprotease B2, which in combination are capable of detoxifying immunogenic gluten peptides in a novel treatment of celiac disease.

Structural genes of wheat and barley 5-methylcytosine DNA glycosylases and their potential applications for human health

“…These proteins cumulatively represent 80% of proteins stored in wheat endosperm and constitute a major source of plant baseddietary proteins consumed worldwide (3). Despite wheat being the major source of dietary proteins, it is also a key determinant of many diet-induced health issues, especially gluten sensitivity, celiac sprue, schizophrenia, dermatitis herpetiformis, and IgE-mediated allergies including anaphylaxis (3)(4)(5). Among these disorders, celiac is one of the most common food-born enteropathies in humans, occurring in various frequencies around the globe (6).…”

“…In HLA DQ2-(or DQ8)-positive individuals, exposure to these gluten proteins can lead to a painful chronic erasure of the microvilli of the epithelium in the intestine and to a permanent intolerance of dietary prolamins (4). The autoimmune response results from the resistance to digestion of proline-/glutamine-rich peptides (epitopes) in the prolamins by gastric, pancreatic, and brush-border membrane proteases.…”

“…Celiac disease is commonly detected in congenital cases with severe symptoms in early childhood. In increasing numbers of patients, symptoms arise only later in life as a result of bread and pasta consumption (4). If untreated, celiac disease may cause increased morbidity and mortality.…”

Immunological effects of transglutaminase-treated gluten in coeliac disease

“…Pivotal for the development of the pathologic process is the interaction between TG2, gluten and gluten-derived peptides [1,18]. The knowledge about this interaction is extremely important for the development of the so-called peptide-based therapies for CD, which aim to substitute the GFD with chemically or genetically modified glutens or derived peptides [11,19,20]. If the introduction of genetically dehydrogenise levels (C) in the medium of cultured duodenal endoscopic biopsies from coeliac patients following a gluten free diet.…”

Diter von Wettstein (Dietrich Holger Wettstein Ritter von Westersheim): September 20, 1929-April 13, 2017

“…He has also genetically engineered barley to achieve strains that are resistant to stem rust fungus, which improved agricultural yields (Horvath et al 2003; Nirmala et al 2011). He received nearly $2 million from the National Institute of Health (NIH), USA, and the Washington Life Science Discovery Fund to develop gluten-free strains of wheat to allow people with celiac disorder to eat food containing wheat flour (Osorio et al 2012). His team generated strains in which 70 to 80% of the glutens, the seed’s storage proteins that cause celiac disease, were successfully removed.…”