Celiac Disease and Immunogenic Wheat Gluten Peptides and the Association of Gliadin Peptides with HLA DQ2 and HLA DQ8

2021 ◽  
pp. 1-24
Author(s):  
Kalekristos Yohannes Woldemariam ◽  
Juanli Yuan ◽  
Zhen Wan ◽  
Qinglin Yu ◽  
Yating Cao ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Wheat Gluten ◽  
Gluten Peptides ◽  
Gliadin Peptides ◽  
Hla Dq2

scholarly journals Celiac disease and its histopathology

2017 ◽  
Vol 7 (1) ◽  
pp. 1118-1123 ◽  
Author(s):  
S Pudasaini
Keyword(s):  
Celiac Disease ◽  
Wheat Gluten ◽  
Duodenal Biopsy ◽  
Inflammatory Disorder ◽  
Small Intestinal Mucosa ◽  
Positive Serology ◽  
Chronic Inflammatory Disorder ◽  
Immune Mediated ◽  
Systemic Manifestations ◽  
Hla Dq2

Celiac disease is gluten induced enteropathy and is a chronic inflammatory disorder of the small intestine characterized by malabsorption. It is a common immune mediated disorder which is triggered by consumption of wheat (gluten). It occurs in genetically predisposed individuals (carriers of HLA-DQ2 and DQ8 haplotypes). It is characterized by inflammation of the small-intestinal mucosa and myriad gastrointestinal and systemic manifestations. A duodenal biopsy with positive serology is the gold standard for the diagnosis of Celiac disease. As there are changing presentation for Celiac disease, communication of pathologist and gastroenterologists is essential for appropriate interpretation of duodenal biopsy.

scholarly journals Prevalence of Celiac Disease and Celiac Autoimmunity in the Toba Native Amerindian Community of Argentina

2015 ◽  
Vol 29 (8) ◽  
pp. 431-434 ◽  
Author(s):  
Horacio Vázquez ◽  
María de la Paz Temprano ◽  
Emilia Sugai ◽  
Stella M Scacchi ◽  
Cecilia Souza ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Tissue Transglutaminase ◽  
Human Leukocyte ◽  
Screen Test ◽  
Leukocyte Antigen ◽  
Day Range ◽  
Gliadin Peptides ◽  
Endomysial Antibodies ◽  
Very High ◽  
Hla Dq2

BACKGROUND: Celiac disease (CD) is mostly recognized among subjects with a Caucasian ethnic ancestry. No studies have explored conditions predisposing Amerindians to CD.OBJECTIVE: To prospectively assess environmental, genetic and serological conditions associated with CD among members of the Toba native population attending a multidisciplinary sanitary mission.METHODS: An expert nutritionist determined daily gluten intake using an established questionnaire. Gene typing for the human leukocyte antigen (HLA) class II alleles was performed on DNA extracted from peripheral blood (HLA DQ2/DQ8 haplotype). Serum antibodies were immunoglobulin (Ig) A tissue transglutaminase (tTG) and the composite deamidated gliadin peptides/tTG Screen test. Positive cases were tested for IgA endomysial antibodies.RESULTS: A total of 144 subjects (55% female) were screened. The estimated mean gluten consumption was 43 g/day (range 3 g/day to 185 g/day). Genetic typing showed that 73 of 144 (50.7%) subjects had alleles associated with CD; 69 (94.5%) of these subjects had alleles for HLA DQ8 and four had DQ2 (5.5%). Four and six subjects had antibody concentrations above the cut-off established by the authors’ laboratory (>3 times the upper limit of normal) for IgA tTG and deamidated gliadin peptides/tTG screen, respectively. Four of these had concomitant positivity for both assays and endomysial antibodies were positive in three subjects who also presented a predisposing haplotype.CONCLUSION: The present study was the first to detect CD in Amerindians. The native Toba ethnic population has very high daily gluten consumption and a predisposing genetic background. We detected subjects with persistent CD autoimmunity and, at least, three of them fulfilled serological criteria for CD diagnosis.

scholarly journals Trehalose Modulates Autophagy Process to Counteract Gliadin Cytotoxicity in an In Vitro Celiac Disease Model

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 348 ◽  
Author(s):  
Federico Manai ◽  
Alberto Azzalin ◽  
Martina Morandi ◽  
Veronica Riccardi ◽  
Lisa Zanoletti ◽  
...  
Keyword(s):  
Celiac Disease ◽  
In Vitro Model ◽  
Wheat Gluten ◽  
Disease Model ◽  
Autoimmune Disorder ◽  
Beneficial Effects ◽  
Gliadin Peptides ◽  
Autophagy Pathway ◽  
Vitro Model

Celiac disease (CD) is a chronic systemic autoimmune disorder that is triggered by the ingestion of gliadin peptides, the alcohol-soluble fraction of wheat gluten. These peptides, which play a key role in the immune response that underlies CD, spontaneously form aggregates and exert a direct toxic action on cells due to the increase in the reactive oxygen species (ROS) levels. Furthermore, peptic-tryptic digested gliadin peptides (PT-gliadin) lead to an impairment in the autophagy pathway in an in vitro model based on Caco-2 cells. Considering these premises, in this study we have analyzed different mTOR-independent inducers, reporting that the disaccharide trehalose, a mTOR-independent autophagy activator, rescued the autophagy flux in Caco-2 cells treated with digested gliadin, as well as improved cell viability. Moreover, trehalose administration to Caco-2 cells in presence of digested gliadin reduced the intracellular levels of these toxic peptides. Altogether, these results showed the beneficial effects of trehalose in a CD in vitro model as well as underlining autophagy as a molecular pathway whose modulation might be promising in counteracting PT-gliadin cytotoxicity.

scholarly journals Structural Perspective of Gliadin Peptides Active in Celiac Disease

2020 ◽  
Vol 21 (23) ◽  
pp. 9301
Author(s):  
Lucia Falcigno ◽  
Luisa Calvanese ◽  
Mariangela Conte ◽  
Merlin Nanayakkara ◽  
Maria Vittoria Barone ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Molecular Mechanisms ◽  
Dimensional Structure ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Polyproline Ii ◽  
Gluten Peptides ◽  
Hla Dq ◽  
Gliadin Peptides ◽  
Adaptive Immune Systems

Gluten fragments released in gut of celiac individuals activate the innate or adaptive immune systems. The molecular mechanisms associated with the adaptive response involve a series of immunodominant gluten peptides which are mainly recognized by human leucocyte antigen (HLA)-DQ2.5 and HLA-DQ8. Other peptides, such as A-gliadin P31–43, are not recognized by HLA and trigger innate responses by several routes not yet well detailed. Among the gluten fragments known to be active in Celiac disease, here we focus on the properties of all gluten peptides with known tri-dimensional structure either those locked into HLA-DQ complexes whose crystals were X-ray analyzed or characterized in solution as free forms. The aim of this work was to find the structural reasons why some gluten peptides prompt the adaptive immune systems while others do not, by apparently involving just the innate immune routes. We propose that P31–43 is a non-adaptive prompter because it is not a good ligand for HLA-DQ. Even sharing a similar ability to adopt polyproline II structure with the adaptive ones, the way in which the proline residues are located along the sequence disfavors a productive P31–43-HLA-DQ binding.

scholarly journals SERONEGATIVE CELIAC DISEASE IN BRAZILIAN PATIENTS: A SERIES OF CASES

2021 ◽  
Author(s):  
Lorete M S KOTZE ◽  
Shirley R R UTIYAMA ◽  
Luiz Roberto KOTZE ◽  
Renato NISIHARA
Keyword(s):  
Celiac Disease ◽  
Clinical Symptoms ◽  
Correct Diagnosis ◽  
Wheat Gluten ◽  
Serum Levels ◽  
Duodenal Mucosa ◽  
Clinical Profile ◽  
Histological Findings ◽  
Duodenal Biopsies ◽  
Hla Dq2

ABSTRACT BACKGROUND: Celiac disease (CD) is an autoimmune disease characterized by immune reaction mostly to wheat gluten. The diagnosis is based on clinical, serological and histological findings in patients ingesting gluten. Cases that the clinical profile indicates CD and the autoantibodies are negative bring so a dilemma for the professional, as the risk of missed the diagnosis or a delay at the same. OBJECTIVE: To show the importance of correct diagnosis of cases with seronegative celiac disease (SNCD). METHODS: Ten cases of SNCD Brazilian patients were retrospectively studied (2013 to 2019). Data of clinical complaints, autoantibodies, IgA serum levels, histological findings and HLA-DQ2/DQ-8 were compiled. Dual-X densitometry, delay at diagnosis, previous autoimmune diseases and family history of CD were also checked. RESULTS: All SNCD patients presented clinical symptoms of CD, with confirmed diagnosis by histological findings of the duodenal mucosa and HLA-DQ2 and/or HLA-DQ8 positivity. All patients had normal IgA levels and negative autoantibodies (IgA-anti-transglutaminase and anti-endomysial). Dual-X densitometry detected osteopenia in two women and osteoporosis in two males, all with low levels of vitamin D. Delay diagnostic ranged from 1 to 19 years. Familiar occurrence of CD was reported in 40% of the cases. After one year of gluten-free diet, eight patients refer improve of symptoms, while duodenal biopsies, done in five cases, showed histological improvement. CONCLUSION: Patients who demonstrate the clinical profile of celiac disease with negative serology and normal levels of IgA, especially those who have family members with celiac disease, should be submitted to duodenal biopsies to look for histological findings.

Modelling of HLA-DQ2 and its interaction with gluten peptides to explain molecular recognition in celiac disease

2005 ◽  
Vol 23 (5) ◽  
pp. 419-431 ◽  
Author(s):  
Susan Costantini ◽  
Mauro Rossi ◽  
Giovanni Colonna ◽  
Angelo M. Facchiano
Keyword(s):  
Celiac Disease ◽  
Molecular Recognition ◽  
Gluten Peptides ◽  
Hla Dq2

scholarly journals Main Chain Hydrogen Bond Interactions in the Binding of Proline-rich Gluten Peptides to the Celiac Disease-associated HLA-DQ2 Molecule

2005 ◽  
Vol 280 (23) ◽  
pp. 21791-21796 ◽  
Author(s):  
Elin Bergseng ◽  
Jiang Xia ◽  
Chu-Young Kim ◽  
Chaitan Khosla ◽  
Ludvig M. Sollid
Keyword(s):  
Hydrogen Bond ◽  
Major Histocompatibility Complex ◽  
Celiac Disease ◽  
Hydrogen Bonds ◽  
Main Chain ◽  
Amide Hydrogen ◽  
Hydrogen Bond Interactions ◽  
Histocompatibility Complex ◽  
Gluten Peptides ◽  
Hla Dq2

Binding of peptide epitopes to major histocompatibility complex proteins involves multiple hydrogen bond interactions between the peptide main chain and major histocompatibility complex residues. The crystal structure of HLA-DQ2 complexed with the αI-gliadin epitope (LQPFPQPELPY) revealed four hydrogen bonds between DQ2 and peptide main chain amides. This is remarkable, given that four of the nine core residues in this peptide are proline residues that cannot engage in amide hydrogen bonding. Preserving main chain hydrogen bond interactions despite the presence of multiple proline residues in gluten peptides is a key element for the HLA-DQ2 association of celiac disease. We have investigated the relative contribution of each main chain hydrogen bond interaction by preparing a series of N-methylated αI epitope analogues and measuring their binding affinity and off-rate constants to DQ2. Additionally, we measured the binding of αI-gliadin peptide analogues in which norvaline, which contains a backbone amide hydrogen bond donor, was substituted for each proline. Our results demonstrate that hydrogen bonds at P4 and P2 positions are most important for binding, whereas the hydrogen bonds at P9 and P6 make smaller contributions to the overall binding affinity. There is no evidence for a hydrogen bond between DQ2 and the P1 amide nitrogen in peptides without proline at this position. This is a unique feature of DQ2 and is likely a key parameter for preferential binding of proline-rich gluten peptides and development of celiac disease.

scholarly journals Dietary Nanoparticles Interact with Gluten Peptides and Alter the Intestinal Homeostasis Increasing the Risk of Celiac Disease

2021 ◽  
Vol 22 (11) ◽  
pp. 6102
Author(s):  
Clara Mancuso ◽  
Francesca Re ◽  
Ilaria Rivolta ◽  
Luca Elli ◽  
Elisa Gnodi ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Metallic Nanoparticles ◽  
Synergistic Effects ◽  
Food Sector ◽  
Intestinal Homeostasis ◽  
Gluten Peptides ◽  
Transmission Electron ◽  
Duodenal Biopsies ◽  
Junction Proteins

The introduction of metallic nanoparticles (mNPs) into the diet is a matter of concern for human health. In particular, their effect on the gastrointestinal tract may potentially lead to the increased passage of gluten peptides and the activation of the immune response. In consequence, dietary mNPs could play a role in the increasing worldwide celiac disease (CeD) incidence. We evaluated the potential synergistic effects that peptic-tryptic-digested gliadin (PT) and the most-used food mNPs may induce on the intestinal mucosa. PT interaction with mNPs and their consequent aggregation was detected by transmission electron microscopy (TEM) analyses and UV–Vis spectra. In vitro experiments on Caco-2 cells proved the synergistic cytotoxic effect of PT and mNPs, as well as alterations in the monolayer integrity and tight junction proteins. Exposure of duodenal biopsies to gliadin plus mNPs triggered cytokine production, but only in CeD biopsies. These results suggest that mNPs used in the food sector may alter intestinal homeostasis, thus representing an additional environmental risk factor for the development of CeD.

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