Interferon Signature in the Blood in Inflammatory Common Variable Immune Deficiency
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE51406 | GEO | 2014/01/09
SECONDARY ACCESSION(S): PRJNA222977
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-01-09 | E-GEOD-51406 | biostudies-arrayexpress
Project description:Transcriptional profiling was used to characterize the immunologic networks in subjects with CVID who have inflammatory complications to identify clues as to pathogenesis and potentially better modes of treatment. CVID subjects who fulfilled the standard diagnostic criteria, including significantly decreased levels of IgG, IgA, and/or IgM and poor or absent specific antibody production were enrolled. They were classified into, with or without characteristic inflammatory complications, as previously designated (hematologic or organ-specific autoimmunity, biopsy-proven granulomatous disease, or interstitial lung disease, lymphoid hyperplasia/ with splenomegaly or gastrointestinal inflammatory disease). 59 patients were included in the training set and 21 healthy controls and for test set 32 patients and 15 healthy controls. Disease controls included 6 X-linked agammaglobulinemia (XLA) patients and 15 healthy controls were included. Blood was taken before the interval intravenous immune globulin (Ig) infusions, or between subcutaneous administrations. The blood was collected using Tempus tubes and processed for microarray analysis.
2014-01-09 | E-GEOD-51404 | biostudies-arrayexpress
Project description:Transcriptional profiling was used to characterize the immunologic networks in subjects with CVID who have inflammatory complications to identify clues as to pathogenesis and potentially better modes of treatment. CVID subjects who fulfilled the standard diagnostic criteria, including significantly decreased levels of IgG, IgA, and/or IgM and poor or absent specific antibody production were enrolled. They were classified into, with or without characteristic inflammatory complications, as previously designated (hematologic or organ-specific autoimmunity, biopsy-proven granulomatous disease, or interstitial lung disease, lymphoid hyperplasia/ with splenomegaly or gastrointestinal inflammatory disease). 59 patients were included in the training set and 21 healthy controls and for test set 32 patients and 15 healthy controls. Disease controls included 6 X-linked agammaglobulinemia (XLA) patients and 15 healthy controls were included. Blood was taken before the interval intravenous immune globulin (Ig) infusions, or between subcutaneous administrations. The blood was collected using Tempus tubes and processed for microarray analysis.
2014-01-09 | E-GEOD-51405 | biostudies-arrayexpress
Project description:Transcriptional profiling was used to characterize the immunologic networks in subjects with CVID who have inflammatory complications to identify clues as to pathogenesis and potentially better modes of treatment.
2014-01-09 | GSE51405 | GEO
Project description:Transcriptional profiling was used to characterize the immunologic networks in subjects with CVID who have inflammatory complications to identify clues as to pathogenesis and potentially better modes of treatment.
2014-01-09 | GSE51404 | GEO
Project description:Common variable immunodeficiency (CVID) is an antibody deficiency treated with immunoglobulin; however, patients can have noninfectious inflammatory conditions that lead to heightened morbidity and mortality.Modular analyses of RNA transcripts in whole blood previously identified an upregulation of many interferon-responsive genes. In this study we sought the cell populations leading to this signature.Lymphoid cells were measured in peripheral blood of 55 patients with CVID (31 with and 24 without inflammatory/autoimmune complications) by using mass cytometry and flow cytometry. Surface markers, cytokines, and transcriptional characteristics of sorted innate lymphoid cells (ILCs) were defined by using quantitative PCR. Gastrointestinal and lung biopsy specimens of subjects with inflammatory disease were stained to seek ILCs in tissues.The linage-negative, CD127(+), CD161(+) lymphoid population containing T-box transcription factor, retinoic acid-related orphan receptor (ROR) ?t, IFN-?, IL-17A, and IL-22, all hallmarks of type 3 innate lymphoid cells, were expanded in the blood of patients with CVID with inflammatory conditions (mean, 3.7% of PBMCs). ILCs contained detectable amounts of the transcription factors inhibitor of DNA binding 2, T-box transcription factor, and ROR?t and increased mRNA transcripts for IL-23 receptor (IL-23R) and IL-26, demonstrating inflammatory potential. In gastrointestinal and lung biopsy tissues of patients with CVID, numerous IFN-?(+)ROR?t(+)CD3(-) cells were identified, suggesting a role in these mucosal inflammatory states.An expansion of this highly inflammatory ILC population is a characteristic of patients with CVID with inflammatory disease; ILCs and the interferon signature are markers for the uncontrolled inflammatory state in these patients.
| S-EPMC4866594 | biostudies-literature
Project description:We used high throughput sequencing to examine the structure and composition of the T cell receptor ? chain in Common Variable Immune Deficiency (CVID). TCR? CDR3 regions were amplified and sequenced from genomic DNA of 44 adult CVID subjects and 22 healthy adults, using a high-throughput multiplex PCR. CVID TCRs had significantly less junctional diversity, fewer n-nucleotide insertions and deletions, and completely lacked a population of highly modified TCRs, with 13 or more V-gene nucleotide deletions, seen in healthy controls. The CVID CDR3 sequences were significantly more clonal than control DNA, and displayed unique V gene usage. Despite reduced junctional diversity, increased clonality and similar infectious exposures, DNA of CVID subjects shared fewer TCR sequences as compared to controls. These abnormalities are pervasive, found in out-of-frame sequences and thus independent of selection and were not associated with specific clinical complications. These data support an inherent T cell defect in CVID.
| S-EPMC4501913 | biostudies-literature
Project description:A Pomeranian dog, 1 year- and 8 month-old neutered female, was presented with persistent respiratory distress and recurrent generalized demodicosis. Physical examination revealed cyanosis, rough respiratory sounds, multifocal alopecia and dermal erosions on the dorsal side of the forelimbs, perineal area and skin around the eyes. A severe diffuse interstitial lung pattern was observed on thoracic radiographs. The blood examination revealed neutrophilia and hypoglobulinemia. Serum immunoglobulin concentrations of IgG and IgA were low. Histopathological examination revealed severe diffuse interstitial pneumonia with Pneumocystis carinii infection. Severe lymphoid depletion was observed in the spleen and other organs with lymphoid follicles consisted mainly of CD3-positive T cells and few cells of B-cell lineage. B-cell hypoplasia with subsequent antibody deficiency was suspected.
| S-EPMC4488410 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-12-11 | GSE220267 | GEO
Project description:Patients with common variable immunodeficiency (CVID) can develop immune dysregulation complications such as autoimmunity, lymphoproliferation, enteritis, and malignancy, which cause significant morbidity and mortality. We aimed to (i) assess the potential of serum proteomics in stratifying patients with immune dysregulation using two independent cohorts and (ii) identify cytokine and chemokine signaling pathways that underlie immune dysregulation in CVID. A panel of 180 markers was measured in two multicenter CVID cohorts using Olink Protein Extension Assay technology. A classification algorithm was trained to distinguish CVID with immune dysregulation (CVIDid, n = 14) from CVID with infections only (CVIDio, n = 16) in the training cohort, and validated on a second testing cohort (CVIDid n = 23, CVIDio n = 24). Differential expression in both cohorts was used to determine relevant signaling pathways. An elastic net classifier using MILR1, LILRB4, IL10, IL12RB1, and CD83 could discriminate between CVIDid and CVIDio patients with a sensitivity of 0.83, specificity of 0.75, and area under the curve of 0.73 in an independent testing cohort. Activated pathways (fold change > 1.5, FDR-adjusted p < 0.05) in CVIDid included Th1 and Th17-associated signaling, as well as IL10 and other immune regulatory markers (LAG3, TNFRSF9, CD83). Targeted serum proteomics provided an accurate and reproducible tool to discriminate between patients with CVIDid and CVIDio. Cytokine profiles provided insight into activation of Th1 and Th17 pathways and indicate a possible role for chronic inflammation and exhaustion in immune dysregulation. These findings serve as a first step towards the development of biomarkers for immune dysregulation in CVID.
| S-EPMC7858548 | biostudies-literature