wheat flour treatment with microbial transglutaminase and lysine ethyl ester: new frontiers in celiac disease treatment.

Conditions: Celiac Disease

Summary: celiac disease is one of the most common forms of food intolerance (prevalence 1/200). the disease occurs in genetically predisposed individuals after ingestion of foods containing gluten. celiac patients can suffer from severe malabsorption syndrome, mainly characterized by diarrhea and weight loss. the only therapeutic approach currently recognized is a life-long gluten-free diet. specific regions of gluten molecule become recognizable by lymphocytes and activate them, due to changes made by tissue transglutaminase. these changes consist in the conversion of specific residues of glutamine into glutamic acid. the consequence is an increased binding affinity between gluten and histocompatibility molecule (hla-dq2), localized on the surface of the "antigen presenting cells" (apc); the exposure of the fragments of modified gluten on the surface of apc is a phenomenon that eventually activates t lymphocytes. recent studies on modified gluten confirmed the hypothesis that it is possible to block the presentation of gluten to lymphocytes by means of lysine ethyl ester binding exclusively to those gluten regions responsible for lymphocyte activation. the enzymatic treatment is performed directly on flour instead of extracted gluten, maintaining the same anti-inflammatory effectiveness. the procedure uses a food-grade enzyme, the microbial transglutaminase (mtgasi) isolated from streptoverticillium mobarensis, able to catalyze the formation of intermolecular "cross-links" that modify the functional properties of the products. objective of the study is to validate the ability of the enzyme treatment of wheat flour with mtgasi and lysine ethyl ester to block the toxic effect of gluten in celiac patients.

celiac disease is one of the most common forms of food intolerance (prevalence 1/200). the disease occurs in genetically predisposed individuals after ingestion of foods containing wheat gluten and similar proteins found in other common cereals such as barley and rye. celiac patients can suffer from severe malabsorption syndrome, mainly characterized by diarrhea, weight loss and growth retardation. the only therapeutic approach currently recognized is a life-long gluten-free diet. specific regions of gluten molecule become recognizable by lymphocytes and activate them, due to changes made by tissue transglutaminase. these changes consist in the conversion of specific residues of glutamine (q) into glutamic acid (e). the consequence is an increased binding affinity between gluten and histocompatibility molecule (hla-dq2), localized on the surface of the "antigen presenting cells" (apc); the exposure of the fragments of modified gluten on the surface of apc is a phenomenon that eventually activates t lymphocytes. recent studies on modified gluten confirmed the hypothesis that it is possible to block the presentation of gluten to lymphocytes by means of lysine ethyl ester binding exclusively to those gluten regions responsible for lymphocyte activation. specifically, it is possible to perform the enzymatic treatment directly on flour instead of extracted gluten, maintaining the same anti-inflammatory effectiveness. the final procedure consists in dissolving the flour in water in the presence of appropriate concentrations of enzyme and lysine ethyl ester, maintaining the suspension in constant motion for two hours at room temperature. the procedure uses a food-grade enzyme, the microbial transglutaminase (mtgasi) isolated from streptoverticillium mobarensis, already used for the preparation of food. the mtgasi is able to catalyze the formation of intermolecular "cross-links" modifying the functional properties of the products through the aggregation and polymerization of proteins. the peculiar method identified by our laboratory reduces the possibility of cross-links between proteins: consequently, minimal changes involve the gluten structure and, consequently, the visco-elastic properties of the dough. objective of the study is to validate the ability of the enzyme treatment of wheat flour with mtgasi and lysine ethyl ester to block the toxic effect of gluten in celiac patients.

Eligibility criteria:
inclusion criteria: inclusion criteria * diagnosis of celiac disease according to espghan criteria: class iii according to marsh-oberhuber classification, clear response to gluten-free diet, serological antiendomysium and antitransglutaminase antibodies positive results before gfd; * hla dq2-dq8 positive results; * gluten-free diet from at least one year; * negative serology from at least 1 year; exclusion criteria * inflammatory bowel diseases; * tumors; * infectious liver disease; * renal impairment.

Keywords: celiac disease gluten-free diet wheat flour treatment microbial transglutaminase lysine ethyl ester celiac disease treatment