scholarly journals Oral Consumption of Bread from an RNAi Wheat Line with Strongly Silenced Gliadins Elicits No Immunogenic Response in a Pilot Study with Celiac Disease Patients

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4548
Author(s):  
María H. Guzmán-López ◽  
Susana Sánchez-León ◽  
Miriam Marín-Sanz ◽  
Isabel Comino ◽  
Verónica Segura ◽  
...  
Keyword(s):  
Immune Response ◽  
Celiac Disease ◽  
Pilot Study ◽  
Mononuclear Cells ◽  
Storage Proteins ◽  
Gastrointestinal Symptoms ◽  
Wheat Line ◽  
Short Term ◽  
Peripheral Blood Mononuclear ◽  
Stool Samples

Celiac disease (CD) is a genetically predisposed, T cell-mediated and autoimmune-like disorder caused by dietary exposure to the storage proteins of wheat and related cereals. A gluten-free diet (GFD) is the only treatment available for CD. The celiac immune response mediated by CD4+ T-cells can be assessed with a short-term oral gluten challenge. This study aimed to determine whether the consumption of bread made using flour from a low-gluten RNAi wheat line (named E82) can activate the immune response in DQ2.5-positive patients with CD after a blind crossover challenge. The experimental protocol included assessing IFN-γ production by peripheral blood mononuclear cells (PBMCs), evaluating gastrointestinal symptoms, and measuring gluten immunogenic peptides (GIP) in stool samples. The response of PBMCs was not significant to gliadin and the 33-mer peptide after E82 bread consumption. In contrast, PBMCs reacted significantly to Standard bread. This lack of immune response is correlated with the fact that, after E82 bread consumption, stool samples from patients with CD showed very low levels of GIP, and the symptoms were comparable to those of the GFD. This pilot study provides evidence that bread from RNAi E82 flour does not elicit an immune response after a short-term oral challenge and could help manage GFD in patients with CD.

scholarly journals Gliadin Sequestration as a Novel Therapy for Celiac Disease: A Prospective Application for Polyphenols

2021 ◽  
Vol 22 (2) ◽  
pp. 595
Author(s):  
Charlene B. Van Buiten ◽  
Ryan J. Elias
Keyword(s):  
Immune Response ◽  
Celiac Disease ◽  
Gastrointestinal Symptoms ◽  
Autoimmune Disorder ◽  
Treatment Method ◽  
Mucosal Damage ◽  
Protective Effects ◽  
Novel Therapy ◽  
Gluten Proteins ◽  
Prospective Application

Celiac disease is an autoimmune disorder characterized by a heightened immune response to gluten proteins in the diet, leading to gastrointestinal symptoms and mucosal damage localized to the small intestine. Despite its prevalence, the only treatment currently available for celiac disease is complete avoidance of gluten proteins in the diet. Ongoing clinical trials have focused on targeting the immune response or gluten proteins through methods such as immunosuppression, enhanced protein degradation and protein sequestration. Recent studies suggest that polyphenols may elicit protective effects within the celiac disease milieu by disrupting the enzymatic hydrolysis of gluten proteins, sequestering gluten proteins from recognition by critical receptors in pathogenesis and exerting anti-inflammatory effects on the system as a whole. This review highlights mechanisms by which polyphenols can protect against celiac disease, takes a critical look at recent works and outlines future applications for this potential treatment method.

scholarly journals Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 514
Author(s):  
Denise Utami Putri ◽  
Cheng-Hui Wang ◽  
Po-Chun Tseng ◽  
Wen-Sen Lee ◽  
Fu-Lun Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Severe Disease ◽  
Viral Rna ◽  
Disease Course ◽  
Peripheral Blood Mononuclear ◽  
Peripheral Immune Cells ◽  
Cell Profile

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

scholarly journals Single-cell multi-omics analysis of the immune response in COVID-19

2021 ◽  
Author(s):  
Emily Stephenson ◽  
◽  
Gary Reynolds ◽  
Rachel A. Botting ◽  
Fernando J. Calero-Nieto ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Single Cell ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Effector Memory ◽  
Peripheral Blood Mononuclear ◽  
Cross Sectional ◽  
Hematopoietic Stem ◽  
Symptomatic Disease

AbstractAnalysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.

Nutritional Management of Celiac Disease

2018 ◽  
Author(s):  
Ciarán P Kelly ◽  
Satya Kurada ◽  
Mariana Urquiaga
Keyword(s):  
Immune Response ◽  
Celiac Disease ◽  
Tight Junction ◽  
Villous Atrophy ◽  
Gastrointestinal Symptoms ◽  
Gluten Free Diet ◽  
Intestinal Biopsy ◽  
Nutritional Management ◽  
Gluten Free ◽  
Antigliadin Antibodies

Celiac disease (CD) is an autoimmune disorder characterized by an immune response to gluten peptides in wheat, barley, and rye. The diagnosis of celiac disease is confirmed by three important characteristics: consistent symptoms, positive celiac-specific serology, and small intestinal biopsy findings of inflammation, crypt hyperplasia, and villous atrophy. CD may present with overt gastrointestinal symptoms, including diarrhea (or constipation), weight loss, and abdominal bloating and discomfort, or covertly with micronutrient deficiencies such as iron deficiency with anemia. A gluten-free diet (GFD) remains the mainstay of treatment. The aim of this review is to highlight the pathogenesis of CD, concepts and challenges associated with a GFD, and nutritional management of CD applicable in clinical practice to internists, gastroenterologists, and dietitians. Patients should be referred to an expert celiac dietitian for education on adherence to a GFD to address gluten contamination in the diet, the psychosocial implications of following a GFD, and macro- and micronutrient disequilibria arising from celiac disease and the GFD. Several novel therapeutics are on the horizon in various stages of development, including glutenases, antigliadin antibodies, tight junction regulators, modulation of the immune response to gliadin, and efforts to engineer less toxic gluten-containing foodstuffs. This review contains 3 figures, 5 tables, and 61 references. Key words: celiac disease, genetic engineering, food engineering, gluten, glutenases, gluten-free diet, oats, IgY, nutrition, tight junction regulators, wheat

scholarly journals LPS-Induced Endotoxemia Evokes Epigenetic Alterations in Mitochondrial DNA That Impacts Inflammatory Response

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2282
Author(s):  
Björn Koos ◽  
Eva Lotta Moderegger ◽  
Katharina Rump ◽  
Hartmuth Nowak ◽  
Katrin Willemsen ◽  
...  
Keyword(s):  
Immune Response ◽  
Mitochondrial Dna ◽  
Dna Methyltransferase ◽  
Protein Import ◽  
Mononuclear Cells ◽  
Mitochondrial Protein ◽  
Mitochondrial Fraction ◽  
Protein Abundance ◽  
Peripheral Blood Mononuclear ◽  
Cellular Expression

Mitochondrial DNA (mtDNA) plays a vital role as a damage-associated molecular pattern in sepsis being able to shape the immune response. Since pathogen recognition receptors of innate immune cells are activated by demethylated DNA only, we set out to investigate the amount of DNA methyltransferase 1 (DNMT1) in mitochondria and the extent of mtDNA methylation in a human endotoxin model. Peripheral blood mononuclear cells of 20 healthy individuals were isolated from whole blood and stimulated with lipopolysaccharide (LPS) for 48 h. Subsequently, DNMT1 protein abundance was assessed in whole cells and a mitochondrial fraction. At the same time, methylation levels of mtDNA were quantified, and cytokine expression in the supernatant was measured. Despite increased cellular expression of DNMT1 after LPS stimulation, the degree of mtDNA methylation slightly decreased. Strikingly the mitochondrial protein abundance of DNMT1 was reduced by 50% in line with the lower degree of mtDNA methylation. Although only modest alterations were seen in the degree of mtDNA methylation, these strongly correlated with IL-6 and IL-10 expression. Our data may hint at a protein import problem for DNMT1 into the mitochondria under LPS stimulation and suggest a role of demethylated mtDNA in the regulation of the inflammatory immune response.

Nutritional Management of Celiac Disease

2017 ◽  
Author(s):  
Ciarán P Kelly ◽  
Satya Kurada ◽  
Mariana Urquiaga
Keyword(s):  
Immune Response ◽  
Celiac Disease ◽  
Tight Junction ◽  
Villous Atrophy ◽  
Gastrointestinal Symptoms ◽  
Gluten Free Diet ◽  
Intestinal Biopsy ◽  
Nutritional Management ◽  
Gluten Free ◽  
Antigliadin Antibodies

Celiac disease (CD) is an autoimmune disorder characterized by an immune response to gluten peptides in wheat, barley, and rye. The diagnosis of celiac disease is confirmed by three important characteristics: consistent symptoms, positive celiac-specific serology, and small intestinal biopsy findings of inflammation, crypt hyperplasia, and villous atrophy. CD may present with overt gastrointestinal symptoms, including diarrhea (or constipation), weight loss, and abdominal bloating and discomfort, or covertly with micronutrient deficiencies such as iron deficiency with anemia. A gluten-free diet (GFD) remains the mainstay of treatment. The aim of this review is to highlight the pathogenesis of CD, concepts and challenges associated with a GFD, and nutritional management of CD applicable in clinical practice to internists, gastroenterologists, and dietitians. Patients should be referred to an expert celiac dietitian for education on adherence to a GFD to address gluten contamination in the diet, the psychosocial implications of following a GFD, and macro- and micronutrient disequilibria arising from celiac disease and the GFD. Several novel therapeutics are on the horizon in various stages of development, including glutenases, antigliadin antibodies, tight junction regulators, modulation of the immune response to gliadin, and efforts to engineer less toxic gluten-containing foodstuffs. This review contains 3 figures, 5 tables, and 61 references. Key words: celiac disease, genetic engineering, food engineering, gluten, glutenases, gluten-free diet, oats, IgY, nutrition, tight junction regulators, wheat

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