Single-cell sequencing of peripheral blood mononuclear cells in acute Kawasaki disease
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE168732 | GEO | 2021/03/12
REPOSITORIES: GEO
Similar Datasets
Project description:To further development of our miRNA diagnostic approach to Kawasaki disease(KD), we have employed microRNA microarray expression profiling as a discovery platform to identify microRNAs as the potential biomarkers to rapidly diagnose Kawasaki disease. Pooled exosome of serum in equal amount from 5 healthy children, 5 KD patients and 5 KD patients after Intravenous immunoglobulin (IVIG) therapy were used for microRNA microarray analysis. MicroRNA profile of exosome from Kawasaki disease(KD) was analyzed by microRNA microarray analysis in 5 healthy children, 5 KD patients and 5 KD patients after IVIG therapy.
2014-09-03 | E-GEOD-60965 | biostudies-arrayexpress
Project description:To further development of our miRNA diagnostic approach to Kawasaki disease(KD), we have employed microRNA microarray expression profiling as a discovery platform to identify microRNAs as the potential biomarkers to rapidly diagnose Kawasaki disease. Pooled exosome of serum in equal amount from 5 healthy children, 5 KD patients and 5 KD patients after Intravenous immunoglobulin (IVIG) therapy were used for microRNA microarray analysis.
2014-09-03 | GSE60965 | GEO
Project description:Infliximab (IFX) has been reported as the further therapy in intravenous immunoglobulin G (IVIG)-resistant Kawasaki disease (KD) patients. IFX is a monoclonal antibody that blocks the pro-inflammatory cytokine tumor necrosis factor (TNF)-α, but how IFX affect KD vasculitis is unknown. We investigated expression profiling of whole blood cells to elucidate the molecular mechanisms of the effectiveness of IFX therapy and to find characteristic biomarker and an important target in refractory KD. Methods: Refractory KD patients who failed to respond to repeated intravenous immunoglobulin G (IVIG) infusions had received a single infusion of IFX as third therapy. To validate specifically transcripts abundance for IFX therapy, we detected the altered transcripts expression and signaling pathways of whole blood mRNA in these IFX-responsive patients (n=8) using Affymetrix array, comparing initial IVIG-responsive patients (n=6).Results: A total of 1,388 transcripts abundance were significantly altered before and after IFX treatment. These transcripts abundance in IFX had Nucleotide-binding oligomerization domain pathway that play a role in activation of NFκB and IL-1 signaling pathway outside the field of TNF-α signaling pathway. Fifty transcripts including Peptidase inhibitor-3 (PI3), Matrix metalloproteinase-8 (MMP8), Chemokine (C-C motif) receptor-2 (CCR2) and Pentraxin-3 (PTX3) were significantly down-regulated in IFX. Conclusion: We demonstrated that the inhibition of TNF-α by IFX have affected various molecular mechanism materially for IVIG-resistant KD patients. 28 samples of pre- and post-treatment in IFX-responsive patients (n=8) and IVIG-responsive patients (n=6).
2014-04-30 | E-GEOD-48498 | biostudies-arrayexpress
Project description:Clinical score and transcript abundance patterns identify Kawasaki disease patients who may benefit from addition of methylprednisolone. Intravenous immunoglobulin (IVIG) treatment-resistant patients are high risk of developing coronary artery lesions (CALs) with Kawasaki disease (KD). The IVIG-responsive (Group A; n = 6) and -resistant patients (Group B) were predicted before starting the initial treatment using the Egami scoring system, and randomly allocated a single-IVIG treatment group (Group B1; n = 6) or a IVIG-plus-methylprednisolone (IVMP) combined therapy group (Group B2; n = 5). We investigated transcript abundance in the leukocytes of those patients using microarray analysis. Results: five patients in Group A and 1 patient in Group B1 responded to initial IVIG treatment. All Group B2 patients responded to IVIP-plus-IVMP combined therapy. Prior to performing these treatments, those transcripts related to IVIG-resistance and to the development of CALs, such as IL1R, IL18R, oncostatin M, suppressor of cytokine signaling-3, S100A12 protein, carcinoembryonic antigen-related cell adhesion molecule-1, matrix metallopeptidase-9 and polycythemia rubra vera-1 were more abundant in Group B patients in comparison to Group A patients. Moreover, those transcripts in Group B2 patients were more profoundly and broadly suppressed than Group B1 patients after treatment. Conclusion: this study elucidated the molecular mechanism of the effectiveness of IVIG-plus-IVMP combined therapy. 34 samples of pre- and post-treatment in three groups consisting of predicted as IVIG-responsive patients, given single-IVIG treatment patients and IVIG-plus-IVMP combined therapy group in predicted as IVIG-resistant patients.
2010-07-08 | E-GEOD-16797 | biostudies-arrayexpress
Project description:Infliximab (IFX) has been reported as the further therapy in intravenous immunoglobulin G (IVIG)-resistant Kawasaki disease (KD) patients. IFX is a monoclonal antibody that blocks the pro-inflammatory cytokine tumor necrosis factor (TNF)-α, but how IFX affect KD vasculitis is unknown. We investigated expression profiling of whole blood cells to elucidate the molecular mechanisms of the effectiveness of IFX therapy and to find characteristic biomarker and an important target in refractory KD. Methods: Refractory KD patients who failed to respond to repeated intravenous immunoglobulin G (IVIG) infusions had received a single infusion of IFX as third therapy. To validate specifically transcripts abundance for IFX therapy, we detected the altered transcripts expression and signaling pathways of whole blood mRNA in these IFX-responsive patients (n=8) using Affymetrix array, comparing initial IVIG-responsive patients (n=6).Results: A total of 1,388 transcripts abundance were significantly altered before and after IFX treatment. These transcripts abundance in IFX had Nucleotide-binding oligomerization domain pathway that play a role in activation of NFκB and IL-1 signaling pathway outside the field of TNF-α signaling pathway. Fifty transcripts including Peptidase inhibitor-3 (PI3), Matrix metalloproteinase-8 (MMP8), Chemokine (C-C motif) receptor-2 (CCR2) and Pentraxin-3 (PTX3) were significantly down-regulated in IFX. Conclusion: We demonstrated that the inhibition of TNF-α by IFX have affected various molecular mechanism materially for IVIG-resistant KD patients.
2014-04-30 | GSE48498 | GEO
Project description:Background: Kawasaki disease (KD) is an acute self-limited vasculitis and the leading cause of acquired heart disease in children in developed countries. No etiologic agent(s) has been identified, and the processes that mediate formation of coronary artery aneurysms and abatement of fever following treatment with intravenous immunoglobulin (IVIG) remain poorly understood. Results: In an initial survey, we used DNA microarrays to examine patterns of gene expression in peripheral whole blood from 20 children with KD; each was sampled during the acute, subacute, and convalescent phases of the illness. Acute KD was characterized by increased relative abundance of gene transcripts associated with innate immune and proinflammatory responses and decreased abundance of transcripts associated with natural killer cells and CD8+ lymphocytes. There was significant temporal variation in transcript levels during the acute disease phase and stabilization thereafter. We confirmed these temporal patterns in a second cohort of 64 patients, and identified additional inter-individual differences in transcript abundance. Notably, higher levels of transcripts of the gene for carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) were associated with an increased percentage of unsegmented neutrophils, fewer days of illness, higher levels of C-reactive protein, and subsequent non-response to IVIG; this last association was confirmed by quantitative reverse transcription PCR in a third cohort of 33 patients, and was independent of day of illness. Conclusions: Acute KD is characterized by dynamic and variable gene-expression programs that highlight the importance of neutrophil activation state and apoptosis in KD pathogenesis. Our findings also support the feasibility of extracting biomarkers associated with clinical prognosis from gene-expression profiles of individuals with systemic inflammatory illnesses. Whole blood (PAXgene tubes) was obtained from 64 Kawasaki disease patients prior to treatment. RNA was amplified using the MessageAmp kit (Ambion), and reverse transcribed. Each sample was labelled with Cy5, and hybridized to a Lymphochip cDNA array along with amplified human reference RNA labelled with Cy3(Universal Human Reference RNA, Stratagene). Analysis was restricted to those array elements (LUIDs) with signal intensity/background of at least 2.5 in either channel for at least 80% of the samples, and a regression correlation of 0.6. Patterns of gene expression were correlated with clinical parameters, including subsequent response to treatment with intravenous immunoglobulin (IVIG). A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Phenotype: Patient responded (R) or not (NR) to IVIG therapy. Some patients were not classified because they were treated more than 10 days after onset of fever Keywords: disease_state_design
2007-12-13 | GSE9864 | GEO
Project description:In this study, we compared global gene expressions between pre- and post- intravenous immunoglobulin (IVIG) administration in nineteen Kawasaki disease (KD) patients. Peripheral blood mononuclear cells (PBMCs) obtained from nineteen patients before and after IVIG treatment was extracted using a PAXgene blood RNA isolation kit. Amplified cRNAs of each patient were analyzed using with Agilent Whole Human Genome Microarray 4x44K G4112F array.
2017-09-19 | GSE73577 | GEO
Project description:Clinical score and transcript abundance patterns identify Kawasaki disease patients who may benefit from addition of methylprednisolone. Intravenous immunoglobulin (IVIG) treatment-resistant patients are high risk of developing coronary artery lesions (CALs) with Kawasaki disease (KD). The IVIG-responsive (Group A; n = 6) and -resistant patients (Group B) were predicted before starting the initial treatment using the Egami scoring system, and randomly allocated a single-IVIG treatment group (Group B1; n = 6) or a IVIG-plus-methylprednisolone (IVMP) combined therapy group (Group B2; n = 5). We investigated transcript abundance in the leukocytes of those patients using microarray analysis. Results: five patients in Group A and 1 patient in Group B1 responded to initial IVIG treatment. All Group B2 patients responded to IVIP-plus-IVMP combined therapy. Prior to performing these treatments, those transcripts related to IVIG-resistance and to the development of CALs, such as IL1R, IL18R, oncostatin M, suppressor of cytokine signaling-3, S100A12 protein, carcinoembryonic antigen-related cell adhesion molecule-1, matrix metallopeptidase-9 and polycythemia rubra vera-1 were more abundant in Group B patients in comparison to Group A patients. Moreover, those transcripts in Group B2 patients were more profoundly and broadly suppressed than Group B1 patients after treatment. Conclusion: this study elucidated the molecular mechanism of the effectiveness of IVIG-plus-IVMP combined therapy.
2010-06-17 | GSE16797 | GEO
Project description:Background: Kawasaki disease (KD) is an acute self-limited vasculitis and the leading cause of acquired heart disease in children in developed countries. No etiologic agent(s) has been identified, and the processes that mediate formation of coronary artery aneurysms and abatement of fever following treatment with intravenous immunoglobulin (IVIG) remain poorly understood. Results: In an initial survey, we used DNA microarrays to examine patterns of gene expression in peripheral whole blood from 20 children with KD; each was sampled during the acute, subacute, and convalescent phases of the illness. Acute KD was characterized by increased relative abundance of gene transcripts associated with innate immune and proinflammatory responses and decreased abundance of transcripts associated with natural killer cells and CD8+ lymphocytes. There was significant temporal variation in transcript levels during the acute disease phase and stabilization thereafter. We confirmed these temporal patterns in a second cohort of 64 patients, and identified additional inter-individual differences in transcript abundance. Notably, higher levels of transcripts of the gene for carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) were associated with an increased percentage of unsegmented neutrophils, fewer days of illness, higher levels of C-reactive protein, and subsequent non-response to IVIG; this last association was confirmed by quantitative reverse transcription PCR in a third cohort of 33 patients, and was independent of day of illness. Conclusions: Acute KD is characterized by dynamic and variable gene-expression programs that highlight the importance of neutrophil activation state and apoptosis in KD pathogenesis. Our findings also support the feasibility of extracting biomarkers associated with clinical prognosis from gene-expression profiles of individuals with systemic inflammatory illnesses. Whole blood RNA (PAXgene tubes) was collected from 20 Kawasaki patients during the acute, sub-acute (post-IVIG treatment) and convalescent phases of the disease. RNA was amplified using the MessageAmp kit (Ambion), and reverse transcribed. Each sample was labelled with Cy5, and hybridized to a Lymphochip cDNA array along with amplified human reference RNA labelled with Cy3(Universal Human Reference RNA, Stratagene). Analysis was restricted to those array elements (LUIDs) with signal intensity/background of at least 2.5 in either channel for at least 80% of the samples, and a regression correlation of 0.6. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Keywords: disease_state_design
2007-12-13 | GSE9863 | GEO
Project description:Background: Kawasaki Disease (KD) is a childhood illness of suspected infectious etiology that causes medium-sized muscular arteritis, most critically affecting the coronary arteries. No single diagnostic test exists, hampering early diagnosis and treatment. Approximately 25% of untreated patients develop coronary artery disease, and children who are treated with intravenous gammaglobulin but do not respond are also at high risk. Subacute/chronic arteritis and luminal myofibroblastic proliferation are the pathologic processes occurring in KD CA after the second week of illness, when neutrophilic necrotizing arteritis has subsided. The specific dysregulated immune pathways contributing to subacute/chronic arteritis have been unknown, hampering the development of effective immunomodulatory therapies for patients not responding to intravenous gammaglobulin therapy. Methods and Results: Deep RNA sequencing was performed on KD (n=8) and childhood control (n=7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Molecular pathways involving T helper cell, cytotoxic T lymphocyte, dendritic cells, and antigen presentation were the most significantly dysregulated. There was significant upregulation of immunoglobulin and type I interferon-stimulated genes. 80 upregulated extracellular genes encoding secreted proteins are candidate biomarkers of KD arteritis. Conclusions: The immune transcriptional profile in KD coronary artery tissues is primarily T helper and cytotoxic lymphocyte-mediated, and has features of an antiviral immune response such as type I interferon-stimulated gene expression. This first report of the KD coronary artery transcriptome identifies specific dysregulated immune response pathways that can inform the development of new therapies for and biomarkers of KD arteritis, and provide direction for future etiologic studies.
2016-04-22 | GSE64486 | GEO