Coeliac Disease-Inducing Gluten
In vitro harmfulness & detoxification by germinating cereal enzymes
Acta Universitatis Tamperensis, No. 1581

By Satumarja Stenman
Febuary 2011
Tampere University Press
Distributed by Coronet Books Inc.
ISBN: 9789514483189
126 pages
$87.50 Paper Original

Coeliac disease is an autoimmune disorder triggered by prolamins of wheat, rye and barley (gliadin, secalin and hordein, respectively). The high content of proline and glutamine residues in the gluten prolamins renders these prolamins highly resistant to human digestive enzymes. In genetically susceptibile individuals this is thought to lead to activation of innate and adaptive immune responses in the small-intestinal mucosa and development of coeliac disease, characterised by mucosal villous atrophy and crypt hyperplasia together with the presence of disease-specific IgA-class autoantibodies. The lifetime disease can currently be treated only by avoidance of wheat, rye and barley, a gluten-free diet.

The purpose of the present study was first to demonstrate the gluten-dependent activation of innate and adaptive immune reactions in several in vitro models in order to investigate the harmfulness of wheat gliadin and rye secalin related to coeliac disease in vitro. It was demonstrated that gliadin and secalin equally stimulate innate immunity-related reactions in Caco-2 epithelial cells, suggesting that rye secalin is as toxic as wheat gliadin also in the early phases of the disease mechanisms and thus preferably to be exluded from the diet of patients suffering from coeliac disease. Moreover, gliadin was observed to stimulate proliferation of coeliac patient-derived small-intestinal mucosal T cells and to activate disease-specific adaptive immune reactions in small-bowel mucosal biopsies from coeliac disease patients. This series further evaluated the relevance of the human small-intestinal organ culture method in the field of coeliac disease research in general. It was observed that biopsy samples from untreated or short-term-treated coeliac disease patients still retaining small-bowel mucosal IgA deposits should be used in order to reliably study the toxic effects of gluten ex vivo.

Furhermore, with a view to develop alternative treatments for coeliac disease by fully detoxifying gluten peptides already prior to their entrance into the small-bowel mucosa, gliadin and secalin were cleaved with germinating cereal enzymes derived from wheat, rye and barley. These proteases naturally effect total hydrolysis of gluten prolamins during the germination process in cereal seeds. In the present studies, gliadin and secalin were efficiently degraded into short fragments by these enzymes. In addition, a reduction in the toxicity of enzymatically pre-treated gliadin and secalin products was observed using the above mentioned coeliac disease-related in vitro models.

In the current studies, gluten toxicity related to coeliac disease in vitro, was evaluated using several overlapping models, including epithelial cells representing innate immunity, T cells related to adaptive immunity, as well as these two linked together in a human organ culture system. These models, gave indications that in the future it will be possible to develop novel medical treatments for the condition by degrading gluten peptides into non-toxic fragments by means of a variety of germinating cereal enzymes. These enzymes may also be relevant in improving the quality and taste of coeliac-safe food products, for example by adding enzymatically pre-treated rye to gluten-free products.

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