Exploring the lncRNAs biomarker which related to IP3/DAG signal pathway leading to mast cells degranulation in chronic spontaneous urticaria
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ABSTRACT:
PROVIDER: PRJNA769408 | ENA |
REPOSITORIES: ENA
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Project description:To determine whether lncRNAs are involved in chronic spontaneous urticaria (CSU), we analyzed the expression profile of lncRNAs and mRNAs in CSU.
2022-01-26 | GSE185516 | GEO
Project description:Chronic spontaneous urticaria (CSU), also traditionally called Chronic Idiopathic Urticaria (CIU), is a common dermatosis. Its estimated point prevalence is 0.6 to 1%. CSU is defined by spontaneously occurring short-lived and itching wheal, angioedema or both. The current nomenclature of urticaria endorses the use of a clinical rather than an aetiological classification to recognise that a percentage of patients with CSU have an autoimmune rather than idiopathic aetiology. As it happens with other IgE-associated diseases, a better knowledge of urticaria patients requires defining phenotypes. The present knowledge about CSU phenotypes is based on the clinical characteristics, associated comorbidities, the course of the disease and its response to the available effective drugs. But a phenotype is defined as the visible characteristics or traits that are a consequence of the expression of genes as well as the influence of environmental factors. The phenotype is part a consequence of the genotype. To study which is the genotype expressed by the patients suffering of CSU can be interesting. The mechanisms involved in the mast cell activation and the role of the released mast cell mediators are well known allowing explaining of how the wheals appear and disappear. But very little is known about the genetic susceptibility and genes involved in the development of wheals in CSU patients. By means of this work, enough case series was collected to draw reliable conclusions, based on the genetic variations found. In order to assess associations between genetic polymorphisms and the different phenotypes of CSU, large case series of well-documented patients with a relevant history are needed. The primary purpose of this study was to identify the most relevant genes expressed in the tissue and the blood samples from patients with moderate and severe CSU.
2017-04-19 | GSE72541 | GEO
Project description:Chronic spontaneous urticaria (CSU), also traditionally called Chronic Idiopathic Urticaria (CIU), is a common dermatosis. Its estimated point prevalence is 0.6 to 1%. CSU is defined by spontaneously occurring short-lived and itching wheal, angioedema or both. The current nomenclature of urticaria endorses the use of a clinical rather than an aetiological classification to recognise that a percentage of patients with CSU have an autoimmune rather than idiopathic aetiology. As it happens with other IgE-associated diseases, a better knowledge of urticaria patients requires defining phenotypes. The present knowledge about CSU phenotypes is based on the clinical characteristics, associated comorbidities, the course of the disease and its response to the available effective drugs. But a phenotype is defined as the visible characteristics or traits that are a consequence of the expression of genes as well as the influence of environmental factors. The phenotype is part a consequence of the genotype. To study which is the genotype expressed by the patients suffering of CSU can be interesting. The mechanisms involved in the mast cell activation and the role of the released mast cell mediators are well known allowing explaining of how the wheals appear and disappear. But very little is known about the genetic susceptibility and genes involved in the development of wheals in CSU patients. By means of this work, enough case series was collected to draw reliable conclusions, based on the genetic variations found. In order to assess associations between genetic polymorphisms and the different phenotypes of CSU, large case series of well-documented patients with a relevant history are needed. The primary purpose of this study was to identify the most relevant genes expressed in the tissue and the blood samples from patients with moderate and severe CSU.
2017-04-19 | GSE72540 | GEO
Project description:Chronic spontaneous urticaria (CSU), also traditionally called Chronic Idiopathic Urticaria (CIU), is a common dermatosis. Its estimated point prevalence is 0.6 to 1%. CSU is defined by spontaneously occurring short-lived and itching wheal, angioedema or both. The current nomenclature of urticaria endorses the use of a clinical rather than an aetiological classification to recognise that a percentage of patients with CSU have an autoimmune rather than idiopathic aetiology. As it happens with other IgE-associated diseases, a better knowledge of urticaria patients requires defining phenotypes. The present knowledge about CSU phenotypes is based on the clinical characteristics, associated comorbidities, the course of the disease and its response to the available effective drugs. But a phenotype is defined as the visible characteristics or traits that are a consequence of the expression of genes as well as the influence of environmental factors. The phenotype is part a consequence of the genotype. To study which is the genotype expressed by the patients suffering of CSU can be interesting. The mechanisms involved in the mast cell activation and the role of the released mast cell mediators are well known allowing explaining of how the wheals appear and disappear. But very little is known about the genetic susceptibility and genes involved in the development of wheals in CSU patients. By means of this work, enough case series was collected to draw reliable conclusions, based on the genetic variations found. In order to assess associations between genetic polymorphisms and the different phenotypes of CSU, large case series of well-documented patients with a relevant history are needed. The primary purpose of this study was to identify the most relevant genes expressed in the tissue and the blood samples from patients with moderate and severe CSU. Objective: The primary purpose of this study was to identify the most relevant genes expressed in the tissue and the blood samples from patients with moderate and severe CSU. The knowledge of the gene profiling differences comparing wheal versus no-lesion skin in selected patients is a real and accurate approach to identify the genes expressed in the wheal developed in patients with CSU. Patients and methods: A total of 20 patients suffering of moderate and severe CSU/CIU and 10 healthy control subjects were included. The setting of the study was the Department of Dermatology and the Department of Pharmacology Clinic at the Hospital del Mar, Institut Mar d'Investigacions Mediques, Barcelona. The sample size is adequate to the exploratory character of the study. Only patients showing active moderate to severe CSU during at least 3 months were included in the study. Patients were selected prospectively. An Urticaria Activity Score (UAS) 7 defined moderate to severe CSU, this mean an UAS7 �16 (UAS 7 range from 0 to 42), where the symptom itch showed a value �8. All the patients included remained symptomatic in spite of the treatment with antihistamines. The diagnosis of CSU was based on clinical history data and physical examination. Any active treatment was supplied at the patient at the time where the samples were obtained. Healthy controls were selected from a pool of volunteers. A detailed anamnesis, clinical exploration and basal blood analysis was carried out in order to guarantee that any active disease nor cutaneous nor systemic was present. The CSU patients and the healthy volunteers were submitted to some interventions in order to obtain cutaneous and venous blood samples. Cutaneous biopsies were obtained after local anesthesia using punch biopsy of 4 mm in diameter. Two cutaneous biopsies including skin from an active wheal and one biopsy from non-lesion skin were obtained. The active wheal chosen for biopsy was obtained from the trunk and clinically showed erythema and edema, with a time of evolution of at least of one hour. One of the biopsies taken from the wheal was fixed in formaldehyde and after paraffin inclusion was stained with haematoxilin -eosin, Giemsa and with c-Kit as mast cell marker with the objective to characterize the diagnosis of wheal and describe accurately the characteristics of the inflammatory infiltrate. The second biopsy was immediately prepared for storage prior to be submitted for gene array. Fat and other undesired components that do not belong to the sample were removed before quick-freezing the tissue in liquid nitrogen. Cryopreserved tissue samples were stored at -80°C prior to the gene microarray study. The punch taken over no-lesion skin guarantee that no wheal was present in the previous 72 hours and no other skin alteration was present i.e., desquamation or pigmentation. Venous blood analysis was obtained from the basilic mediana vein in the antecubital fossae and prepared for its storage for gene array analysis. Quality control of RNA samples was performed with the Bioanalyzer 2100 (Agilent Technologies, Palo Alto, CA, USA). Good quality samples with an RNA Integrity Number (RIN) value >6, and also some mildly degraded samples with a RIN value between 4 and 6, were processed following specific protocols. The hybridization procedure was performed according to the Agilent 60-mer oligo microarray processing protocol using the Agilent Gene Expression Hybridization Kit (Agilent Technologies). Based on the results provided from the microarray comparative analysis, we selected a set of genes to be confirmed by Q-PCR. The criteria followed to perform such selection were based in technical aspects that would guarantee gene confirmation. These recommendations include an adjusted P value of 0.05 and a Log fold change of 1 (plus or minor to 1). The second criteria was based in an accurate analysis of the genes up or down regulated and its possible involvement in mast cell biology, wheal pathogenesis, urticaria or allergy. The data base included shows the raw data of the gene-array performed in the available samples of the blood and the tissue of the patients with CSU and the healthy controls included in this study. 61 samples were analyzed from 30 individuals, 20 patients and 10 healthy controls. This Series includes the samples from tissue.
2017-04-19 | E-GEOD-72540 | biostudies-arrayexpress
Project description:Chronic spontaneous urticaria (CSU), also traditionally called Chronic Idiopathic Urticaria (CIU), is a common dermatosis. Its estimated point prevalence is 0.6 to 1%. CSU is defined by spontaneously occurring short-lived and itching wheal, angioedema or both. The current nomenclature of urticaria endorses the use of a clinical rather than an aetiological classification to recognise that a percentage of patients with CSU have an autoimmune rather than idiopathic aetiology. As it happens with other IgE-associated diseases, a better knowledge of urticaria patients requires defining phenotypes. The present knowledge about CSU phenotypes is based on the clinical characteristics, associated comorbidities, the course of the disease and its response to the available effective drugs. But a phenotype is defined as the visible characteristics or traits that are a consequence of the expression of genes as well as the influence of environmental factors. The phenotype is part a consequence of the genotype. To study which is the genotype expressed by the patients suffering of CSU can be interesting. The mechanisms involved in the mast cell activation and the role of the released mast cell mediators are well known allowing explaining of how the wheals appear and disappear. But very little is known about the genetic susceptibility and genes involved in the development of wheals in CSU patients. By means of this work, enough case series was collected to draw reliable conclusions, based on the genetic variations found. In order to assess associations between genetic polymorphisms and the different phenotypes of CSU, large case series of well-documented patients with a relevant history are needed. The primary purpose of this study was to identify the most relevant genes expressed in the tissue and the blood samples from patients with moderate and severe CSU. Objective: The primary purpose of this study was to identify the most relevant genes expressed in the tissue and the blood samples from patients with moderate and severe CSU. The knowledge of the gene profiling differences comparing wheal versus no-lesion skin in selected patients is a real and accurate approach to identify the genes expressed in the wheal developed in patients with CSU. Patients and methods: A total of 20 patients suffering of moderate and severe CSU/CIU and 10 healthy control subjects were included. The setting of the study was the Department of Dermatology and the Department of Pharmacology Clinic at the Hospital del Mar, Institut Mar d'Investigacions Mediques, Barcelona. The sample size is adequate to the exploratory character of the study. Only patients showing active moderate to severe CSU during at least 3 months were included in the study. Patients were selected prospectively. An Urticaria Activity Score (UAS) 7 defined moderate to severe CSU, this mean an UAS7 �16 (UAS 7 range from 0 to 42), where the symptom itch showed a value �8. All the patients included remained symptomatic in spite of the treatment with antihistamines. The diagnosis of CSU was based on clinical history data and physical examination. Any active treatment was supplied at the patient at the time where the samples were obtained. Healthy controls were selected from a pool of volunteers. A detailed anamnesis, clinical exploration and basal blood analysis was carried out in order to guarantee that any active disease nor cutaneous nor systemic was present. The CSU patients and the healthy volunteers were submitted to some interventions in order to obtain cutaneous and venous blood samples. Cutaneous biopsies were obtained after local anesthesia using punch biopsy of 4 mm in diameter. Two cutaneous biopsies including skin from an active wheal and one biopsy from non-lesion skin were obtained. The active wheal chosen for biopsy was obtained from the trunk and clinically showed erythema and edema, with a time of evolution of at least of one hour. One of the biopsies taken from the wheal was fixed in formaldehyde and after paraffin inclusion was stained with haematoxilin -eosin, Giemsa and with c-Kit as mast cell marker with the objective to characterize the diagnosis of wheal and describe accurately the characteristics of the inflammatory infiltrate. The second biopsy was immediately prepared for storage prior to be submitted for gene array. Fat and other undesired components that do not belong to the sample were removed before quick-freezing the tissue in liquid nitrogen. Cryopreserved tissue samples were stored at -80°C prior to the gene microarray study. The punch taken over no-lesion skin guarantee that no wheal was present in the previous 72 hours and no other skin alteration was present i.e., desquamation or pigmentation. Venous blood analysis was obtained from the basilic mediana vein in the antecubital fossae and prepared for its storage for gene array analysis. Quality control of RNA samples was performed with the Bioanalyzer 2100 (Agilent Technologies, Palo Alto, CA, USA). Good quality samples with an RNA Integrity Number (RIN) value >6, and also some mildly degraded samples with a RIN value between 4 and 6, were processed following specific protocols. The hybridization procedure was performed according to the Agilent 60-mer oligo microarray processing protocol using the Agilent Gene Expression Hybridization Kit (Agilent Technologies). Based on the results provided from the microarray comparative analysis, we selected a set of genes to be confirmed by Q-PCR. The criteria followed to perform such selection were based in technical aspects that would guarantee gene confirmation. These recommendations include an adjusted P value of 0.05 and a Log fold change of 1 (plus or minor to 1). The second criteria was based in an accurate analysis of the genes up or down regulated and its possible involvement in mast cell biology, wheal pathogenesis, urticaria or allergy. The data base included shows the raw data of the gene-array performed in the available samples of the blood and the tissue of the patients with CSU and the healthy controls included in this study. 61 samples were analyzed from 30 individuals, 20 patients and 10 healthy controls. This Series includes the samples from blood.
2017-04-19 | E-GEOD-72541 | biostudies-arrayexpress
Project description:Background: Chronic spontaneous urticaria (CSU) is a common, debilitating skin disorder characterised by recurring episodes of raised, itchy and sometimes painful wheals lasting longer than 6 weeks. CSU is mediated by mast cells which are absent from peripheral blood. However, lineage-CD34hiCD117int/hiFcεRI+ cells in blood have previously been shown to represent a mast cell precursor. Methods: We enumerated FcεRI-, FcεRI+ and FcεRIhi lineage-CD34+CD117+ cells using flow cytometry in blood of patients with CSU (n=55), including 12 patients receiving omalizumab and 43 not receiving omalizumab (n=43). Twenty-two control samples were studied. Disease control and patient response to omalizumab was evaluated using the Urticaria Control Test. We performed single cell RNA sequencing (scRNA-seq) on lineage-CD34hiCD117hi blood cells from a subset of patients with CSU (n=8) and healthy controls (n=4). Results: CSU patients had more Lineage-CD34+CD117+FcεRI+ blood cells than controls. Lineage-CD34+CD117+FcεRI+ cells were significantly higher in patients with CSU who had an objective clinical response to omalizumab when compared to patients who had poor disease control 90 days after initiation of omalizumab. scRNA-seq revealed that lineage-CD34+CD117+FcεRI+ cells contained both lymphoid and myeloid progenitor lineages, with omalizumab responsive patients having proportionally more myeloid progenitors. The myeloid progenitor lineage contained small numbers of true mast cell precursors along with more immature FcεRI- and FcεRI+ myeloid progenitors. Conclusion: Increased blood CD34+CD117+FcεRI+ cells may reflect enhanced bone marrow egress in the setting of CSU. High expression of these cells strongly predicts better clinical responses to the anti-IgE therapy, omalizumab.
2024-04-30 | GSE261424 | GEO
Project description:MicroRNA 155 (miR-155) has been shown to regulate the gene expression of important players of physiological and pathological processes, like hematopoietic lineage differentiation, immunity and inflammation, viral infections, cancer and cardiovascular diseases, among others. Degranulation is an event in which mast cells, upon activation of the FceRI, release their granule content rich in vasoactive amines, proteases and TNFa. Additionally activation of the receptor promotes de novo synthesis of cytokines, chemokines and growth factors. Analysis of bone marrow derived mast cells (BMMC) deficient in miR-155 showed a significant increase in FceRI mediated degranulation and in the release of cytokines like TNFa, IL-6 and IL-13. In addition miR 155-/- mice presented higher anaphylaxis reactions compared to WT mice. Gene expression analysis of BMMC was performed in order to identify intermediaries of FceRI mediated degranulation under the control of miR-155. The results indicate that miR-155 regulates negatively the expression of the regulatory subunits of the kinase PI3Kgamma, Pik3r5 (p101) and Pik3r6 (p84, p87PIKAP), involved in Ca+ influx and degranulation. Total RNA from 3 independent cultures of WT and miR-155-/- BMMC treated with anti-DNP IgE and 20 ng/ml DNP-HSA for 1hr were used to performed gene expression analysis using the Affymetrix GenechipM-BM-. Mouse Gene 1.0 ST
2014-03-20 | E-GEOD-56030 | biostudies-arrayexpress
Project description:Mast cells, activated by antigen via the high affinity receptor for IgE (FcεRI), release an array of pro-inflammatory mediators that contribute to allergic disorders such as asthma and anaphylaxis. The KIT ligand, stem cell factor (SCF), is critical for mast cell expansion, differentiation and survival, and, under acute conditions, enhances mast cell activation. However, extended SCF exposure in vivo conversely protects against fatal antigen-mediated anaphylaxis. In investigating this dichotomy, we identified a novel mode of regulation of the mast cell activation phenotype through SCF-mediated programming. We found that mouse bone marrow-derived mast cells chronically exposed to SCF displayed a marked attenuation of FcεRI-mediated degranulation and cytokine production. The hypo-responsive phenotype was not a consequence of altered signals regulating calcium flux or protein kinase C, but of ineffective cytoskeletal reorganization, with evidence implicating a down-regulation of expression of the Src kinase Hck. Collectively, these findings demonstrate a major role for SCF in the homeostatic control of mast cell activation with potential relevance to mast cell-driven disease and the development of novel approaches for the treatment of allergic disorders. Mouse bone marrow-derived mast cells were treated with IL3, IL3+IL33, or IL3+SCF. Six replicates each.
2012-05-01 | E-GEOD-35332 | biostudies-arrayexpress
Project description:Mast cells are tissue resident granulocytes which are most abundant at the interface between tissues and the external environment, such as around blood vessels, in the skin or mucosal surfaces in the lungs and gut. Pathologically they are involved in allergic reactions and anaphylaxis, however they may also play protective roles in responses to some infections, particularly to pathogenic helminths. Mast cells also express high levels of the IL-33 receptor, which like TLRs, activates Myd88 dependent signalling pathways to drive de novo cytokine production in mast cells.IL-33 is a member of the IL-1 family known to stimulate a number of immune cell types including mast cells. IL-33 is a strong activator of de novo cytokine production in mast cells without inducing degranulation, although it has also been shown to synergise with other signals to promote degranulation. Bone Marrow-Derived Mast cells (BMMCs) were cultured as described previously [27]. Briefly, bone marrow was flushed in PBS and the cells pelleted by centrifugation. Cells were cultured at 1 million cells per ml in RPMI 1640 supplemented with 10% FBS (Biosera/Labtech), 5 mM l‐Glutamine (GIBCO Life Technologies), 100 U/ml Penicillin (GIBCO Life Technologies), 100 μg/ml Streptomycin (GIBCO Life Technologies), 25 mM HEPES (Lonza), 1 mM sodium pyruvate (Lonza), 1X nonessential amino acids (Lonza), 50 μM 2‐mercaptoethanol and 30 ng/ml IL‐3 (PeproTech). Cells were passaged twice per week and used between passage 12 and 16. 4 independent BMMC cultures were either stimulated with 10 ng/ml IL-33 for 48 hours or left unstimulated, followed by single shot LC-MS analysis.
2023-03-11 | PXD033759 | Pride
Project description:Mast cells are phenotypically and functionally highly heterogeneous, and their state is possibly controlled by their local microenvironment. Therefore, concrete analyses are needed to understand whether mast cells act as powerful motivators or dispensable bystanders in specific diseases. Here, we evaluated the correlation between synovial mast cells and rheumatoid arthritis (RA) disease severity, and the efficacy of therapeutic interventions against mast cells. We showed that degranulation of mast cells in inflammatory synovial tissues of RA patients was induced via MAS-related G protein-coupled receptor X2 (MRGPRX2), and the expression of MHC class II (MHC II) and costimulatory molecules on mast cells were upregulated. These unique signaling response led to mast cell activation and promoted T cell responses, resulting in the progression of RA. Collagen-induced arthritis mouse models treated with a combination of anti-IL-17A and cromolyn sodium, a mast cell membrane stabilizer, showed significantly reduced clinical severity and decreased bone erosion. The findings of the present study suggest that synovial microenvironment-influenced mast cells contribute to RA and may provide a novel mast cell-targeting therapy for RA.
2024-01-07 | PXD038584 | Pride