Ancestral Wheat Types Release Fewer Celiac Disease Related T Cell Epitopes than Common Wheat upon Ex Vivo Human Gastrointestinal Digestion

Abstract

Celiac disease (CeD) is an autoimmune enteropathy triggered by immunogenic gluten peptides released during the gastrointestinal digestion of wheat. Our aim was to identify T cell epitope-containing peptides after ex vivo digestion of ancestral (einkorn, spelt and emmer) and common (hexaploid) wheat (Fram, Bastian, Børsum and Mirakel) using human gastrointestinal juices. Wheat porridge was digested using a static ex vivo model. Peptides released after 240 min of digestion were analyzed by liquid chromatography coupled to high-resolution mass spectrometry (HPLC-ESI MS/MS). Ex vivo digestion released fewer T cell epitope-containing peptides from the ancestral wheat varieties (einkorn (n = 38), spelt (n = 45) and emmer (n = 68)) compared to the common wheat varieties (Fram (n = 72), Børsum (n = 99), Bastian (n = 155) and Mirakel (n = 144)). Neither the immunodominant 33mer and 25mer α-gliadin peptides, nor the 26mer γ-gliadin peptide, were found in any of the digested wheat types. In conclusion, human digestive juice was able to digest the 33mer and 25mer α-gliadin, and the 26mer γ-gliadin derived peptides, while their fragments still contained naive T cell reactive epitopes. Although ancestral wheat released fewer immunogenic peptides after human digestion ex vivo, they are still highly toxic to celiac patients. More general use of these ancient wheat variants may, nevertheless, reduce CeD incidence.

Ancient and Modern Cereals as Ingredients of the Gluten-Free Diet: Are They Safe Enough for Celiac Consumers?

“…Most studies on the safety of cereals in celiac patients investigate the products after peptic–tryptic digestion (PTd) [ 25 ]. The outcomes most frequently considered are: agglutination, the secretion of cytokines or the alteration of transepithelial electrical resistance (TEER) in cell models, such as Caco-2 cells [ 26 , 27 , 28 ], K562 (S) cells [ 26 , 29 ], or gliadin reactive T-cell lines [ 23 , 30 , 31 , 32 , 33 ].…”

“…In addition, no influence on these parameters by environmental factors, such as the harvest year and N fertilization was observed [20,22]. In a study by Asledottir et al (2020) after an ex vivo digestion, the ancestral cereals (T. monococcum, T. aestivum ssp. spelta and T. diccocum) released fewer T-cell epitope-containing peptides than the common wheat varieties [25].…”

“…In a study by Asledottir et al (2020) after an ex vivo digestion, the ancestral cereals (T. monococcum, T. aestivum ssp. spelta and T. diccocum) released fewer T-cell epitope-containing peptides than the common wheat varieties [25]. However, at present, ancestral wheat is considered toxic for celiac patients.…”

A high-affinity human TCR-like antibody detects celiac disease gluten peptide–MHC complexes and inhibits T cell activation

“…However, detection would require that the patients have maintained a gluten-containing diet until the time of gastroendoscopy. In addition, differences in wheat strains and -gliadin gene content used for food (44), as well as individual variation in ability to proteolytically digest gluten (45), are factors that might underpin the lack of staining in some of the CeD patient samples. mAb 3.C11 specifically inhibited T cell activation and proliferation in vitro and in vivo.…”

Fatty Acid Composition of Grain of Einkorn and Its Relatives

“…Presently, T. monococcum is only grown in some locations of the Mediterranean area. However, some studies demonstrated that T. monococcum boasts other advantages such as low-immunogenic gluten [3,8], low contents of amylase/trypsin-inhibitors [10], high contents of protein [12], lutein and tocols [4,13,26], carotenoids [2,4], resistant starch [4], polyphenolic antioxidants [16], trace elements (selenium) [16]. Einkorn wholemeal flour is rich in lipids (mostly unsaturated fatty acids) [12,17].…”