Project description:This collection of samples were genotyped to use altogether with other data to gain insight into the mechanism behind celiac disease.
Project description:Celiac disease is a chronic immune-mediated disorder with an important genetic component. To date, there are 57 independent association signals from 39 non-HLA loci, and a total of 66 candidate genes have been proposed. We aimed to scrutinize the functional implication of 45 of those genes by analyzing their expression in the disease tissue of celiac patients (at diagnosis/treatment) compared to non-celiac controls. The sample set consisted of 15 CD children at diagnosis (on a gluten-containing diet, with CD associated antibodies, atrophy of intestinal villi and crypt hyperplasia), and the same patients in remission after being treated with GFD for >2 years (asymptomatic, antibody negative, and normalized intestinal epithelium at that time), plus 15 tissue samples from non-celiac individuals not suffering from inflammation at the time of endoscopy used as controls
Project description:Potential celiac diseasase (PCD) is characterized by a positive celiac disease (CD) serology and a normal small intestinal mucosa. This particular condition is usually considered a clinical challenge because, although its diagnostic criteria are clear, many questions are still unsettled. Therefore, given that PCD is a valuable biological model of the pathway leading to small intestinal mucosal damage in genetically predisposed individuals, the aim of our study is to evaluate whether immunological, microbial and lipid signatures could better characterize the PCD from the CD condition.
Project description:The goal of this study was to study the effect of genetic variation on gene expression of untouched primary leucocytes. This expression data is used in conjunction with genome-wide association genotype data that is available for the celiac disease samples, typed on the Illumina Infinium HumanHap300 platform. All genotype data are available upon request.
Project description:Celiac disease is an intestinal inflammatory disorder induced by dietary gluten in genetically susceptible individuals. The mechanisms underlying the massive expansion of interferon g–producing intraepithelial cytotoxic T lymphocytes (CTLs) and the destruction of the epithelial cells lining the small intestine of celiac patients have remained elusive. We report massive oligoclonal expansions of intraepithelial CTLs that exhibit a profound genetic reprogramming of natural killer (NK) functions. These CTLs aberrantly expressed cytolytic NK lineage receptors, such as NKG2C, NKp44, and NKp46, which associate with adaptor molecules bearing immunoreceptor tyrosine-based activation motifs and induce ZAP-70 phosphorylation, cytokine secretion, and proliferation independently of T cell receptor signaling. This NK transformation of CTLs may underlie both the self-perpetuating, gluten-independent tissue damage and the uncontrolled CTL expansion leading to malignant lymphomas in severe forms of celiac disease. Because similar changes were detected in a subset of CTLs from cytomegalovirus-seropositive patients, we suggest that a stepwise transformation of CTLs into NK-like cells may underlie immunopathology in various chronic infectious and inflammatory diseases. Keywords: NKG2C; LAK; CTL; NK receptor; IEL; Mucosal Immunity; Celiac Disease
Project description:microRNAs were profiled in healthy controls, classic celiac patients (CD), CD patients with anemia and GFD treated CD with normalization of duodenal mucosa all CD conditions were related to controls. For each group, five patients were pooled. One replicate per experiment