Duodenal inflammation in Common variable immunodeficiency has altered transcriptional response to viruses
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE207243 | GEO | 2022/11/03
REPOSITORIES: GEO
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Project description:Based on the findings of increased IEL in duodenal biopsies in CVID, an overlap with celiac disease has been suggested. In the present study, increased IEL, in particular in the pars descendens of the duodenum, was one of the most frequent histopathological finding. We therefore examined the gene expression profile in pars descendens of duodenum in CVID patients with increased IEL (n=13, IEL mean 34 [range 22-56] IEL/100 EC), CVID with normal levels of IEL (n=7), celiac disease (n=10, Marsh grade 3a or above) and healthy controls (n=17) by gene expression microarray GI histopathological findings in 53 CVID patients that underwent upper and lower endoscopic examination were addressed. For the microarray analysis 20 CVID (7 CVID_normal and 13 CVID with incresed IEL), 10 patients with celiac diseases and 17 healthy controls were included.
2015-09-02 | E-GEOD-72625 | biostudies-arrayexpress
Project description:We performed a comparison of transcriptome between follicular CD8 T cells (CXCR5+CD8+CD3+) from 3 lymph nodes of patients with common variable immunodeficiency (CVID) and 3 tonsils of healthy donors, discovering 67 differentially expressed genes that show immunoregulatory potential of CVID follicular CD8 T cells.
2019-09-27 | GSE138076 | GEO
Project description:Autoantibody-mediated cytopenias (AICs) regularly occur in profoundly IgG-deficient common variable immunodeficiency (CVID) patients. The isotypes, antigenic targets, and origin(s) of disease-causing autoantibodies in this patient population are unclear. Herein, we report that erythrocytes and platelets from CVID patients with AICs (CVID+AIC) are coated with autoreactive IgM. Glycan array-based analyses of CVID+AIC plasma IgM revealed narrow reactivities to erythrocytic I/i antigens and platelet expressed I/i antigen-related glycans but starkly lower binding to hundreds of other pathogen and tumor-associated carbohydrates. Polyclonal B-cell receptors with corresponding I/i antigen reactivities were highly enriched among CVID+AIC circulating marginal zone (MZ) B cells. Within secondary lymphoid tissues, MZ B cells secreted copious IgM when activated by IL-10 secreting FOXP3-CD25hiTfh cells. In lymph nodes from immunocompetent controls, MZ B cells localized outside of GCs near rare FOXP3-CD25+ cells and plentiful FOXP3+ regulatory T cells. In CVID+AIC lymph nodes, counterpart cells localized to similar anatomic positions but CD25hiTfh cells greatly outnumbered regulatory T cells. In total, our findings indicate glycan-reactive IgM autoantibodies produced outside of GC borders may contribute to the autoimmune pathogenesis of CVID.
2023-06-09 | GSE233753 | GEO
Project description:The homeostasis of circulating B cell subsets in the peripheral blood of healthy adults is well regulated, but in disease it can be severely disturbed. Thus, a subgroup of patients with common variable immunodeficiency (CVID) presents with an extraordinary expansion of an unusual B cell population characterized by the low expression of CD21. Since these circulating atypical B cells in the blood of CVID patients could not be assigned to any certain B cell differentiation stage in the periphery, they were designated as CD21low B cells. Although, CD21low B cells are polyclonal and unmutated IgM+IgD+ B cells like naive B cells in the peripheral blood, they reveal several distinct phenotypic and functional features. In order to uncover the the global programme of gene expression underlying these differences and changes in CD21low B cells we have performed microarray hybridization experiments and identified differentially expressed genes which define a distinct gene expression profile in CD21low B cells compared to naive B cells. Leucocytes were separated by Ficoll gradient from peripheral blood of healthy donors (HD) and CVID patients. CD19+CD27-CD38+CD21+ naive B cells of HD as well as naive and CD19hiCD27-CD38lowCD21low (CD21low) B cells of CVID patients were sorted using a MoFlow cell sorter. RNA was extracted from sorted ex vivo B cell subpopulations and hybridized on Affymetrix microarrays. Gene expression profiles were compared between CD21low B cells and naive B cells of CVID patients as well as HD naive B cells.
2009-07-30 | E-GEOD-17269 | biostudies-arrayexpress
Project description:Based on the findings of increased IEL in duodenal biopsies in CVID, an overlap with celiac disease has been suggested. In the present study, increased IEL, in particular in the pars descendens of the duodenum, was one of the most frequent histopathological finding. We therefore examined the gene expression profile in pars descendens of duodenum in CVID patients with increased IEL (n=12, IEL mean 34 [range 22-56] IEL/100 EC), CVID with normal levels of IEL (n=8), celiac disease (n=10, Marsh grade 3a or above) and healthy controls (n=17) by gene expression microarray
2015-09-02 | GSE72625 | GEO
Project description:The homeostasis of circulating B cell subsets in the peripheral blood of healthy adults is well regulated, but in disease it can be severely disturbed. Thus, a subgroup of patients with common variable immunodeficiency (CVID) presents with an extraordinary expansion of an unusual B cell population characterized by the low expression of CD21. Since these circulating atypical B cells in the blood of CVID patients could not be assigned to any certain B cell differentiation stage in the periphery, they were designated as CD21low B cells. Although, CD21low B cells are polyclonal and unmutated IgM+IgD+ B cells like naive B cells in the peripheral blood, they reveal several distinct phenotypic and functional features. In order to uncover the the global programme of gene expression underlying these differences and changes in CD21low B cells we have performed microarray hybridization experiments and identified differentially expressed genes which define a distinct gene expression profile in CD21low B cells compared to naive B cells.
2009-07-30 | GSE17269 | GEO
Project description:The methylation profiles of bisulfite-modified DNA of CD19+ cells from MZ twins discordant for CVID were compared using the Infinium HumanMethylation450 BeadChips (Illumina, Inc., San Diego, CA,). This platform allows the interrogation of >485,000 methylation sites per sample at single-nucleotide resolution, and comprises an average of 17 CpG sites per gene in the 99% of RefSeq genes. 96% of CpG islands are covered, with additional coverage in CpG island shores and the regions flanking them. The samples were hybridized in the array following the manufacturer’s instructions. Total DNA isolated by standard procedures from CD19+ cells (total B lymphocytes) corresponding to two monozygotic twins discordant for common variable immunodeficiency.
2015-06-17 | E-GEOD-63849 | biostudies-arrayexpress
Project description:Common variable immunodeficiency (CVID), characterized by recurrent infections, low serum class-switched immunoglobulin isotypes and poor antigen specific antibody responses, comprises a heterogeneous patient population in terms of clinical presentation and underlying etiology. The diagnosis is regularly associated with a severe decrease of germinal center (GC) derived B-cell populations in peripheral blood. However, data from B-cell differentiation within GC is limited. We present a multiplex approach combining histology, flow cytometry and B-cell receptor repertoire analysis of sorted GC B-cell populations allowing the modelling of distinct disturbances in GCs of three CVID patients. Our results reflect pathophysiological heterogeneity underlying the reduced circulating pool of post-GC memory B cells and plasmablasts in the three patients. In patient 1, quantitative and qualitative B-cell development in GCs is relatively normal. In patient 2, irregular shaped GCs are associated with reduced somatic hypermutation (SHM), antigen selection and class-switching, while in patient 3, high SHM, impaired antigen selection and class-switching with large single clones imply increased re-cycling of cells within the irregular shaped GCs. In lymph nodes of patients 2 and 3, only limited numbers of memory B cells and plasma cells are formed. While reduced numbers of circulating post GC B cells is a general phenomenon in CVID, the integrated approach exemplified distinct defects during GC maturation ranging from near normal morphology and function to severe disturbances with different facets of impaired maturation of memory B cells and/or plasma cells. Integrated dissection of disturbed GC B-cell maturation by histology, flowcytometry and BCR repertoire analysis reveals essential steps during memory formation.
2022-09-19 | GSE213361 | GEO
Project description:Common variable immunodeficiency (CVID) is the most common form of primary immunodeficiency with an estimated incidence of 1:10,000. It has been apparent for many years that CVID has a genetic component, occurs frequently in families and can have both a recessive or dominant mode of inheritance. In recent years, 4 genes underlying CVID have been identified; however, mutations within in them are estimated to account for no more than 10% of all cases of CVID.
We have identified a multi-generational family with autosomal dominant CVID. Genome-wide linkage analysis has mapped the locus underlying CVID in this family to an approximately 9.2 Mb interval on chromosome 3q27.3-q29, between the markers D3S3570 and D3S1265. This locus is distinct from any of the previously mapped susceptibility loci suggesting a novel genetic variant is responsible for disease in this family. The aim of this study is to use exome sequencing of affected (n = 4) and unaffected (n = 4) individuals, in tandem with the available genetic mapping data, to identify the causal variant underlying CVID in this family.
| EGAS00001000269 | EGA
Project description:An investigation of rare genetic variants in patients presenting with Common Variable Immunodeficiency
2022-04-11 | PRJEB52220 | EVA