72d3218a-f29a-40e9-bbc7-2730d3c9f149 - samples
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ABSTRACT:
PROVIDER: EGAD00001004481 | EGA |
REPOSITORIES: EGA
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Project description:To study V-gene usage among antigen-specific and non-antigen-specific serum IgA antibodies in celiac disease patients, purified antibody fractions were subjected to proteomic analysis. Patients either had eastablished, untreated disease with severe intestinal inflammation or "potential" celiac disease characterized by presence of antibodies but no or mild inflammation. Quantification of the fraction of antibodies using different IGHV segments revealed that antibodies specific to the autoantigen transglutaminase 2 (TG2) displayed a bias toward usage of IGHV5-51 in agreement with previous observations. The fraction of antibodies using IGHV5-51 correlated with the degree of intestinal inflammation, indicating that production of hallmark IGHV5-51 anti-TG2 antibodies coincides with onset of clinical celiac disease.
2019-07-09 | PXD013777 | Pride
Project description:Comparison of serum and gut antibodies against two major antigens in celiac disease patients, the autoantigen transglutaminase 2 (TG2) and a deamidated gluten peptide (DGP) from food. The antigen-specific antibodies were affinity-purified from isolated total IgA of serum or gut biopsy secretions or from whole serum samples. Individual clonotypes could be identified among the purified antibodies based on matching to a database of IgH sequences obtained from antigen-specific gut plasma cells of the same patients.
2017-07-14 | MSV000081328 | MassIVE
Project description:Paired immunoglobulin heavy and light chain sequences were obtained from 803 single IgA plasma cells isolated from duodenal biopsies of five celiac disease patients. The cells were specific to discrete antigenic regions of the enzyme TG2, which is the main autoantigen in celiac disease.
| EGAD00001005029 | EGA
Project description:Objective: Plasma cells (PCs) are terminally differentiated B-lymphocytes that produce antibodies. The lamina propria of the small intestine is particularly rich in PCs. In coeliac disease (CeD) there is infiltration and increased density of PCs in the small intestinal lesion. Many of these PCs produce disease-specific autoantibodies targeting the enzyme transglutaminase 2 (TG2). The plasmacytosis and high numbers of disease-antigen reactive PCs in CeD motivated us to study the transcriptional programme of PCs from coeliac gut lesions.
Design: We performed RNASeq analysis of IgA+ PCs of untreated CeD patients being specific or non-specific for TG2 and from healthy controls.
| EGAS00001003345 | EGA
Project description:Disease-specific plasma cells (PCs) reactive with transglutaminase 2 (TG2) or deamidated gluten peptides (DGP) are abundant in celiac disease (CeD) gut lesions. Their contribution toward CeD pathogenesis is unclear. We assessed expression of markers associated with PC longevity in 15 untreated and 26 treated CeD patients in addition to 13 non-CeD controls, and performed RNA-sequencing with clonal inference and transcriptomic analysis of 3251 single PCs. We observed antigen-dependent V-gene selection and stereotypic antibodies. Generation of recombinant DGP-specific antibodies revealed a key role of a heavy-chain residue that displays polymorphism, suggesting that immunoglobulin gene polymorphisms may influence CeD-specific antibody responses. We identified transcriptional differences between CeD-specific vs non-disease-specific PCs and between short-lived vs long-lived PCs. The short-lived CD19+CD45+ phenotype dominated in untreated and short-term-treated CeD, in particular among disease-specific PCs but also in the general PC population. Thus, the disease lesion of untreated CeD is characterized by massive accumulation of short-lived PCs that are not only directed against disease-specific antigens.
| EGAS00001004623 | EGA
Project description:Celiac disease (CD) is a chronic inflammation of the small intestine triggered by the ingestion of gluten in genetically predisposed individuals. Tissue transglutaminase (TG2) is a key factor in the pathogenesis of CD, because it catalyzes both the deamidation of specific glutamine residues and the formation of covalent Nε-(γ-glutamyl)-lysine isopeptide crosslinks resulting in TG2-gluten peptide complexes. These complexes are thought to activate B cells causing the secretion of anti-TG2 autoantibodies that serve as diagnostic markers for CD, although their pathogenic role remains unclear. To gain more insight into the molecular structures of TG2-gluten peptide complexes, we developed a reciprocal proteomic analysis strategy, which facilitates the comprehensive identification of isopeptides in a complex protein hydrolysate. The workflow consists of four steps: (1) performance of the model reaction between TG2 and gluten peptide(s) followed by tryptic hydrolysis, clean-up and untargeted nLC-MS/MS analysis (2), prediction of tryptic TG2-derived lysine peptides that serve as potential isopeptide modifications (3) the search for isopeptides by configuring the TG2-modifications in MaxQuant and search against the α-gliadin fasta file and (4) the reciprocal search for isopeptides by configuring the gluten peptide(s) as modification in MaxQuant and search against the TG2 fasta file. After verification by manual data curation and visualization, this strategy enabled the identification of 26 different isopeptides involving 19 TG2 lysine residues, only six of which were known previously. Experiments with different TG2-gluten peptide molar ratios revealed that K-425, K-590, K-600 and K-649 were the most preferred lysine residues involved in isopeptide crosslinking. Further, expanding the model system to three gluten peptides allowed the localization of the preferred glutamine crosslinking sites. The described strategy is generally applicable to any hydrolysate containing isopeptides and these new insights into the structure of TG2-gluten peptide complexes may help clarify the role of extracellular TG2 in CD autoimmunity and in other inflammatory diseases.
2019-09-27 | PXD014067 | Pride
Project description:We collected 19 duodenal biopsies of children and adults with celiac disease and compared the expression of 38 selected genes between each other and with the observed in 13 non-celiac disease controls matched by age. qPCR gene expression profiling. Intestinal samples from children and adults with active celiac disease patients and controls were analysed.
2015-12-19 | E-GEOD-76168 | biostudies-arrayexpress
Project description:Patients with Celiac Disease, first degree relatives of celiac patients and control groups displayed significant differential gene expression.
2019-03-21 | GSE112102 | GEO
Project description:The alpha gliadins are a complex group of proteins with very similar sequences that comprise about 15-20% of the total flour protein and contribute to the functional properties of wheat flour dough. Some alpha gliadins also contain immunodominant epitopes relevant to celiac disease, a chronic autoimmune disease that affects nearly 1.4% of the worldwide population. In an attempt to reduce the immunogenic potential of wheat flour in the U.S. spring wheat cultivar Butte 86, RNA interference was used to silence a subset of alpha gliadin genes encoding proteins containing celiac disease epitopes. Two of the resulting transgenic lines were analyzed in detail by quantitative two-dimensional gel electrophoresis combined with tandem mass spectrometry. Although only some genes were targeted by the RNA interference construct, all alpha gliadins were effectively silenced in the transgenic plants. Some off-target silencing of high molecular weight glutenin subunits also was detected in both transgenic lines even though there was no homology with the target sequence. Reactivities of IgG and IgA serum antibodies from a cohort of patients with confirmed cases of celiac disease were decreased in flour from the two transgenic lines relative to the non-transgenic line. However, functional properties of the flour were also altered in the transgenic lines as evidenced by decreases in both mixing times and SDS sedimentation values. Although it may be possible to reduce the immunogenic potential of the flour and retain the viscoelastic properties essential for the utilization of wheat by eliminating only the most immunogenic alpha gliadins, the data suggest that it will be very difficult to selectively silence specific genes within families as complex as the wheat alpha gliadins.
2020-02-28 | PXD016930 | Pride
Project description:Background and aims: Celiac disease is provoked by gluten exposure, but the resultant pathogenic process in the duodenum is not well understood. We aimed to define the core celiac transcriptomic signature and pathologic pathways in pre-treatment diagnostic duodenum biopsies. Methods: We use mRNAseq to define pre-treatment diagnostic duodenum gene expression in 54 pediatric celiac patients and non-celiac controls, and we validate our key findings in an independent cohort of 40 participants. We further define similar and divergent genes and pathways in 177 Crohn disease patients and controls. Results: We observe a marked suppression of mature epithelial metabolic functions in celiac patients, overlapping substantially with the Crohn signature. A marked adaptive immune response was noted for the up-regulated signature including interferon response, alpha-beta, and gamma-delta T-cells that overlapped to some extant with the Crohn signature. However, we identified a celiac specific signature linked to increased cell proliferation, nuclear division, and cell cycle activity that was localized primarily to the epithelia as noted by CCNB1 and Ki67 staining. Lastly, we demonstrate the utility of the transcriptomic date to correctly classify disease or healthy states in the discovery and validation cohorts. Conclusion: Our data provide insights into celiac pathogenesis and can stimulate new approaches to address this highly prevalent condition.
2020-04-10 | GSE131705 | GEO