Lack of immunogenicity of hydrolysed wheat flour in patients with coeliac disease after a short‐term oral challenge

Mandile, Roberta; Picascia, Stefania; Parrella, Claudia; Camarca, Alessandra; Gobbetti, Marco; Greco, Luigi; Troncone, Riccardo; Gianfrani, Carmen; Auricchio, Renata

doi:10.1111/apt.14175

Cited by 32 publications

(24 citation statements)

References 28 publications

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“…In line with previous studies, [ 28,34 ] we observed a large individual variability in the level of IFN‐γ production among the CD volunteers. A variable number of IFN‐γ SFC was detected in the PBMCs even before the gluten intake started (day 0).…”

Section: Discussionsupporting

confidence: 92%

“…In order to address this hypothesis, we further analyzed the capability of TM and TA gluten challenge to mobilize T cells reactive to five immune‐dominant epitopes from α‐ , ω‐ , and γ‐gliadins in a subgroup of CD volunteers. Despite a wide individual variability in the profile of recognized peptides, that is compatible with previous studies, [ 28,34,36 ] overall, we observed that the TM challenge elicited a reduced number of epitope specific T cells. In more details, the patients eating TM bread had a lower frequency of IFN‐γ secreting cells reactive to DQ2.5‐glia α1a/b/α2 epitopes, harbored in the known 33‐mer peptide, in contrast to patients eating TA bread.…”

Section: Discussionsupporting

confidence: 92%

“…This is more likely due to the basal activation of the lymphocytes in these subjects, despite the clinical remission and the gluten‐free diet, as reported in other studies. [ 28,34 ] On the other hand, we cannot exclude that other no‐gluten proteins, in particular those named ATIs, might stimulate an immune response in our CD patients who underwent the wheat challenge. However, recent studies and our unpublished data reported a very lower amount of ATIs in T. monococcum than in T. aestivum .…”

Section: Discussionmentioning

confidence: 99%

“…Noteworthy, the SGC has been recently applied to assess the efficacy of novel therapeutic strategies for the treatment of CD. [ 28–30 ] In the present study, two cohorts of celiac patients compliant to GFD were monitored for cytokine production by the enzyme‐linked immunospot (EliSpot) assay and by quantitative real‐time PCR, before and after the SGC with TM or TA bread.…”

Section: Introductionmentioning

confidence: 99%

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In Celiac Disease Patients the In Vivo Challenge with the Diploid Triticum monococcum Elicits a Reduced Immune Response Compared to Hexaploid Wheat

Picascia

Camarca

Malamisura³

et al. 2020

Molecular Nutrition Food Res

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Scope Gluten from the diploid wheat Triticum monococcum (TM) has low content of immunostimulatory sequences and a high gastro‐intestinal digestibility. Gluten‐reactive T cells elicited by diploid and hexaploid (Triticum aestivum‐TA) wheat in celiac disease (CD) patients upon a brief oral challenge are analyzed. Methods and results Seventeen patients with CD (median age 13 years) consumed for 3 days sandwiches made with TM (cultivar Norberto‐ID331, N=11), or TA (cultivar Sagittario, N=11) flours, corresponding to 12 gr of gluten/die. Immunostimulatory properties are assessed in blood by measuring the IFN‐γ‐secreting T cells by EliSpot and the expression of inflammatory cytokines/receptors (IL‐12A, IL‐15, IL‐18RAP, IFN‐γ) by qPCR. TA mobilizes a remarkable number of gliadin‐specific, IFN‐γ‐secreting T cells (p<0.05), while no significant cell mobilization is induced by TM (p=ns). Similar results are obtained in response to five immunogenic peptides from α‐, ω‐, and γ‐gliadins, although with a large individual variability. An increased mRNA expression for IL‐12A and IFN‐γ is detected in the group eating TA compared to those consuming TM (p<0.05). Conclusions Although T. monococcum is a cereal not suitable for the diet of celiacs, this diploid wheat elicits a reduced in vivo T‐cell response compared to T. aestivum in celiac patients.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In Celiac Disease Patients the In Vivo Challenge with the Diploid Triticum monococcum Elicits a Reduced Immune Response Compared to Hexaploid Wheat

Picascia

Camarca

Malamisura³

et al. 2020

Molecular Nutrition Food Res

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“…En los IELs, se encuentran tres poblaciones mayoritarias de células: linfocitos con TCR α/β + CD8 + , linfocitos con TCR / + y células NK. Aunque solo en el caso de los linfocitos TCR α/β + CD8 + pudo observarse una respuesta específica (Mandile et al 2017;Mazzarella et al 2008). En conjunto, estas células son activadas por IFNs tipo I e IFN, reconocen señales de estrés celular expresadas por los enterocitos y son inductores de apoptosis de enterocitos (Olaussen et al 2002).…”

Section: Mecanismos De Muerte Celular Asociados a Enfermedad Celíacaunclassified

Inducción de mecanismos de la respuesta innata por péptidos de gliadinas en un modelo de enteropatía experimental

Castro¹,

Florencia²

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El gluten es una mezcla heterogénea de proteínas, principalmente gliadinas y gluteninas, que al ser ingerido es degradado por enzimas del tracto gastrointestinal. Algunos péptidos derivados de gluten son resistentes a la degradación enzimática y pueden encontrarse en el lumen intestinal y desencadenar respuestas inmunes tanto adaptativas, como innatas. Entre los péptidos derivados de gliadina resistentes a la degradación se encuentra el péptido p31-43, que no se une a moléculas de MHC de clase II y en consecuencia no es capaz de inducir una respuesta adaptativa específica. Existen numerosos estudios in vitro acerca de la toxicidad de p31-43, sin embargo, en la actualidad se desconoce su receptor celular y no se han descripto en profundidad sus efectos in vivo. En el presente trabajo de tesis se utilizó un modelo murino de enteropatía inducida mediante la administración intraluminal de p31-43, así como también se desarrolló un modelo de administración de p31-43 por vía intragástrica, de modo de estudiar mecanismos de la respuesta innata en intestino delgado. En este modelo intentamos reproducir algunos aspectos de la patogenia de enfermedad celíaca (EC). Esta es una enteropatía crónica que se desencadena en individuos genéticamente predispuestos ante el consumo de proteínas de gluten y bajo la influencia de otros factores ambientales. EC tiene una prevalencia global del 1 % y se caracteriza por la presencia de atrofia vellositaria e hiperplasia de criptas en intestino delgado, así como también, por un marcado incremento en el infiltrado linfocitario en lamina propria y en el epitelio intestinal. En este trabajo de tesis se observó que la enteropatía murina inducida, es específica de la secuencia de aminoácidos de p31-43 y dependiente de la vía de IFN tipo I. Además, corroboramos que p31-43 induce apoptosis tanto in vitro, como in vivo. Por otro lado, se caracterizó las propiedades estructurales y de agregación de p31-VI 43. Se observó que posee una estructura del tipo poliprolina II y que forma agregados proteicos en solución estables a pHs intestinales (3-8), cuyo tamaño se incrementa con la concentración y evolucionan en el tiempo a estructuras más complejas. Finalmente, observamos que las moléculas de NLRP3 y Caspasa-1 estaban implicadas en el daño. Por lo que consideramos que los agregados de p31-43 podrían ser sensados por el inflamasoma NLRP3 y ejercer efectos inflamatorios vía Caspasa-1.

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The Sourdough Microbiota and Its Sensory and Nutritional Performances

Ameur¹,

Arora²,

Polo³

et al. 2022

Good Microbes in Medicine, Food Production, Biotechnology, Bioremediation, and Agriculture

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The era of sourdough fermentation came into existence since the ancient times with continuous developments owing to the scientific community. The role of starter lactic acid bacteria and yeasts, constituting the sourdough microbiota, is undeniable in imparting characteristic nutritional and functional features to the sourdough. This complex community is influenced by sourdough ingredients (flour, water and other additional ingredients) and the house microbiota leading to an optimized protocol for its preparation and propagation. The potential of many non-conventional cereals (legumes, pseudocereals etc.) and milling by-products (wheat germ, bran etc.) has been exploited in this regard for sustainable agriculture and food security. Sourdough fermentation evidently improved the nutritional attributes, in terms of mineral bioavailability, dietary fibers, protein digestibility, antioxidant activity, phenol content etc. while decreasing the antinutritional factors (phytic acid, raffinose, condensed tannins and trypsin inhibitor activity), glycemic index and gluten content. The supplementation of sourdough markedly enhanced the rheology, shelf life and sensory properties as well, thereby, increasing the functional value of baked goods. Nevertheless, a holistic 'Omics' approach is in progress to better understand the metabolic interactions among the 'sourdough fermentome'. This will endeavor us to further comprehend the stability and performance of sourdough technology applied in the baking industry.

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Lack of immunogenicity of hydrolysed wheat flour in patients with coeliac disease after a short‐term oral challenge

Cited by 32 publications

References 28 publications

In Celiac Disease Patients the In Vivo Challenge with the Diploid Triticum monococcum Elicits a Reduced Immune Response Compared to Hexaploid Wheat

In Celiac Disease Patients the In Vivo Challenge with the Diploid Triticum monococcum Elicits a Reduced Immune Response Compared to Hexaploid Wheat

Inducción de mecanismos de la respuesta innata por péptidos de gliadinas en un modelo de enteropatía experimental

The Sourdough Microbiota and Its Sensory and Nutritional Performances

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