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Natural Variation in Toxicity of Wheat

by luciano

Natural Variation in Toxicity of Wheat: Potential for Selection of Nontoxic Varieties for Celiac Disease Patients (and useful for disease prevention in individuals at risk)
Liesbeth Dekking, Harry Jonker et al. Article in Gastroenterology · October 2005. DOI: 10.1053/j.gastro.2005.06.017 · Source: PubMed

“Background & Aims: Celiac disease (CD) is an intestinal disorder caused by T-cell responses to peptides derived from the gluten proteins present in wheat. Such peptides have been found both in the gliadin and glutenin proteins in gluten. The only cure for CD is a lifelong gluten-free diet. It is unknown, however, if all wheat varieties are equally harmful for patients. We investigated whether wheat varieties exist with a nat- ural low number of T-cell–stimulatory epitopes. Methods: Gluten proteins present in public databases were analyzed for the presence of T-cell–stimulatory sequences. In addition, wheat accessions from diploid (AA, SS/BB, and DD genomes), tetraploid (AABB), and hexaploid (AABBDD) Triticum species were tested for the presence of T-cell–stimulatory epitopes in gliadins and glutenins by both T-cell and monoclonal anti-body–based assays. Results: The database analysis readily identified gluten proteins that lack 1 or more of the known T-cell–stimulatory sequences. Moreover, both the T-cell– and antibody-based assays showed that a large variation exists in the amount of T-cell– stimulatory peptides present in the wheat accessions. Conclusions: Sufficient genetic variation is present to endeavor the selection of wheat accessions that con- tain low amounts of T-cell–stimulatory sequences. Such materials may be used to select and breed wheat varieties suitable for consumption by CD patients, contributing to a well-balanced diet and an increase in their quality of life. Such varieties also may be useful for disease prevention in individuals at risk.”

The study also recalls the influence of gluten intake on early childhood nutrition:

“It is known that early exposure to gluten and a double HLA-DQ2 gene dose both promote CD development. In Sweden the addition of gluten to infant food led to a 5-fold increase in the occurrence of CD in the 1980s,and HLA-DQ2 homozygous individuals have a 5-fold increased risk for developing CD com pared with HLA-DQ2 heterozygous individuals. A large repertoire of abundant immunogenic gluten peptides in the diet, together with a high copy number of HLA-DQ2, thus favors the breaking of oral tolerance. In present-day practice, gluten is introduced into the diet of infants at 6–7 months of age. Because there is no restriction in the amount of gluten given, gluten intake at age 12 months is between 6 and 9 g/day, whereas gluten-specific T cells of CD patients are known to respond to microgram amounts. The sudden introduction of grams of gluten thus may play an important role in the breaking of oral tolerance. As we have suggested previously, the current understand- ing of the development of the disease may call for a more gradual and/or reduced intake of gluten in infants. The breeding of wheat varieties with a lower amount of T-cell–stimulatory gluten peptides potentially could aid in reaching that goal.”

….omissis “Wheat gluten is a group of proteins that can be partitioned into 2 protein families: the glutenins and the gliadins. The glutenins can be subdivided further into high molecular weight (HMW) and low molecular weight (LMW) glutenins and the gliadins can be divided into α, γ and ω gliadins. At present, many gluten- derived T-cell–stimulatory peptides are known and they originate from the α, and γ-gliadins, and the HMW and LMW glutenins. Homologue sequences are found in the secalins of rye, the hordeins of barley, and the avenins of oats. Gluten and gluten-like molecules thus contain many immunogenic peptides. Moreover, the unique food-industrial properties of gluten are in part related to a very high proline content that renders gluten relatively resistant to enzymatic degradation in the gastrointestinal tract. Hence, many of the immunogenic gluten peptides are likely to survive for extended periods in the intestine, increasing the probability of triggering a T-cell response. Thus, the unique properties of gluten are linked tightly to their disease- inducing potential in CD patients”.

Celiac disease is a prevalent disorder characterized by a chronic intestinal inflammation driven by HLA-DQ2 or -DQ8-restricted T cells specific for ingested wheat gluten peptides. The dominant T-cell responses are to epitopes that cluster within a stable 33mer fragment formed by physiologic digestion of distinct alpha-gliadins. Celiac disease is treated by excluding all gluten proteins from the diet. Conceivably, a diet based on baking-quality gluten from a wheat species that expresses no or few T-cell stimulatory gluten peptides should be equally well tolerated by the celiac patients and, importantly, also be beneficial for disease prevention. To identify baking quality, harmless wheat, we followed the evolution of the wheat back to the species that most likely have contributed the AA, BB, and DD genomes to the bread wheat. Gluten were extracted from a large collection of these ancient wheat species and screened for T-cell stimulatory gluten peptides. Distinct differences in the intestinal T-cell responses to the diploid species were identified. Interestingly, we found that the fragments identical or equivalent to the immunodominant 33mer fragment are encoded by alpha-gliadin genes on the wheat chromosome 6D and thus absent from gluten of diploid einkorn (AA) and even certain cultivars of the tetraploid (AABB) pasta wheat. These findings have implications for celiac disease because they raise the prospect of identifying or producing by breeding wheat species with low or absent levels of harmful gluten proteins.
Mapping of Gluten T-Cell Epitopes in the Bread Wheat Ancestors: Implications for Celiac Disease. Tore Jensen et al. March 2005 Gastroenterology 128(2):393-401; DOI:10.1053/j.gastro.2004.11.003

Cutaneous Manifestations of Non-Celiac Gluten Sensitivity

by luciano

Cutaneous Manifestations of Non-Celiac Gluten Sensitivity: Clinical Histological and Immunopathological Features
Veronica Bonciolini, Beatrice Bianchi, Elena Del Bianco, Alice Verdelli, and Marzia Caproni
Background: The dermatological manifestations associated with intestinal diseases are becoming more frequent, especially now when new clinical entities, such as Non-Celiac Gluten Sensitivity (NCGS), are identified. The existence of this new entity is still debated. However, many patients with diagnosed NCGS that present intestinal manifestations have skin lesions that need appropriate characterization. Methods: We involved 17 patients affected by NCGS with non-specific cutaneous manifestations who got much better after a gluten free diet. For a histopathological and immunopathological evaluation, two skin samples from each patient and their clinical data were collected. Results: The median age of the 17 enrolled patients affected by NCGS was 36 years and 76% of them were females. On the extensor surfaces of upper and lower limbs in particular, they all presented very itchy dermatological manifestations morphologically similar to eczema, psoriasis or dermatitis herpetiformis. This similarity was also confirmed histologically, but the immunopathological analysis showed the prevalence of deposits of C3 along the dermo-epidermal junction with a microgranular/granular pattern (82%). Conclusions: The exact characterization of new clinical entities such as Cutaneous Gluten Sensitivity and NCGS is an important objective both for diagnostic and therapeutic purposes, since these are patients who actually benefit from a GFD (Gluten Free Diet) and who do not adopt it only for fashion.
….omissis: 5.

At the moment, the results of our study do not allow the exact characterization of a new skin disease related to NCGS. The skin lesions observed were similar both to eczema and psoriasis and did not show a specific histological pattern. Furthermore, no serological marker was useful to identify these patients. The only data common to most of these patients affected by NCGS associated to non-specific skin manifestations are:
1. the itching;
2. the presence of C3 at the dermoepidermal junction;
3. a rapid resolution of lesions when adopting the gluten free diet.”

From: Nutrients. 2015 Sep; 7(9): 7798–7805. Published online 2015 Sep 15. doi:10.3390/nu7095368