In Situ Gluten–Chitosan Interlocked Self‐Assembled Supramolecular Architecture Reduces T‐Cell‐Mediated Immune Response to Gluten in Celiac Disease

Abstract

Scope The prevalence of celiac disease has increased since the last half of the 20th century and is now about 1% in most western populations. At present, people who suffer from celiac disease have to follow a gluten‐exclusion diet throughout their lives. Compliance to this restrictive diet is demanding and the development of alternative strategies has become urgent. Methods and results In this context, it is found that the biocompatible aminopolysaccharide chitosan imposes a different gluten reorganization after gluten redox reaction producing in situ mechanically interlocked supramolecular assemblies between gluten and chitosan. These new structures result in the decrease of gluten digestibility, tissue transglutaminase deamidation activity, and interferon‐γ production in intestinal T cell lines generated from biopsy specimens of celiac disease patients. Conclusion Overall, the results demonstrate the potential of this research avenue to celiac disease is problematic, as the reorganization of gluten proteins to a novel supramolecular architecture shows a positive impact on known pathogenesis mechanisms of the disease. At present, the only therapy for celiac disease is adherence to a gluten‐free diet. Here, it is shown that chitosan‐imposed gluten reorganization to an interlocked self‐assembled supramolecular architecture reduces gluten digestibility, R5‐reactivity, tissue transglutaminase deamidation activity, and its capacity to stimulate a T‐cell‐mediated immune response in celiac disease.

Genetic and Environmental Factors Associated to Glutenin Polymer Characteristics of Wheat

“…The maximum size sieving permitted by chromatography columns is around 1 × 10 6 Da, whereas polymer Mw higher than 1 × 10 7 g/mol have been reported for GPPs [19,20]. The A4F-MALLS of GPP was used in several approaches, such as studying the quality stability of hybrid wheats over different environments [21], the influence of ozone treatment on wheat proteins and quality [22], or the effect of chitosan treatment on gluten proteins [23]. Using A4F-MALLS the influence of the genetic and/or environmental factors have initially reported [20] by studying in a limited set of cultivars grown on two years multilocal trials in France.…”

Celiac Disease: Disease Models in Understanding Pathogenesis and Search for Therapy

“…The strategy of the supramolecular assembly was successful in decreasing gluten digestibility and its capacity to stimulate a T-cell-mediated immune response. This type of tunable approach is a promising nanotechnology tool to change biomaterials features as their immunogenicity [93].…”

Review of Structural Features and Binding Capacity of Polyphenols to Gluten Proteins and Peptides In Vitro: Relevance to Celiac Disease

“…More recently, it was showed that the interaction between gluten proteins and the aminopolyssacharide chitosan imposes a different gluten reorganization resulting in novel supramolecular structures. This novel supramolecular architecture decreased gluten digestibility, TG2 activity and the ability of gluten to stimulate a T-Cell-mediated immune response [ 12 , 40 ].…”

“…In this context, alternative approaches need to be addressed to overcome the biopsychosocial burden in celiac disease [ 11 ]. Some promising approaches took the advantage of knowing the primary trigger of celiac disease, the gluten, and tried to detoxify it: by means of genetic modification as the genetically modified low-gliadin wheat lines, using gluten specific proteases to deliver a complete digestion of immunogenic peptides, using microbial transglutaminase to hamper the deamidation process performed by tissue transglutaminase (TG2) [ 5 ] and even through the sequestration of gliadin proteins or peptides by a novel gluten molecular re-organization [ 12 ] or after ingestion by the use of synthetic polymeric binders in order to decrease gliadin digestibility [ 13 ]. Despite the promising results, including clinical trials, none of these alternative therapies is being used in celiac disease [ 5 ].…”