Global gene expression profiling identifies new therapeutic targets in acute Kawasaki disease
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE63881 | GEO | 2014/12/06
SECONDARY ACCESSION(S): PRJNA269335
REPOSITORIES: GEO
Similar Datasets
Project description:Transcriptional profile in Kawasaki patients at acute and convalescent phase with different clinical outcomes were investigated. To gain further insight into the molecular mechanisms underlying KD, we investigated the acute and convalescent whole blood transcriptional profiles of 171 KD subjects and compared them with the transcriptional profiles of pediatric patients with confirmed bacterial or viral infection, and with healthy control children. We also investigated the transcript abundance in patients with different intravenous immunoglobulin treatment responses and different coronary artery outcomes.
2014-12-06 | E-GEOD-63881 | biostudies-arrayexpress
Project description: Not available
| S-EPMC4279699 | biostudies-other
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:Kawasaki disease (KD) is considered the main contributor to acquired heart diseases in developed countries. However, the precise pathogenesis of KD remains unclear. Neutrophils played roles in KD. This study aimed to select hub genes in neutrophils in acute KD. mRNA microarray of neutrophils from four acute KD patients and three healthy controls was performed to screen differentially expressed mRNAs (DE-mRNAs). DE-mRNAs were analyzed and predicted by Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways, and protein-protein interaction networks. Real time-PCR was finally conducted to confirm the reliability and validity of the expression level of DE-mRNAs from blood samples of healthy controls and KD patients in both acute and convalescent stage.
2023-02-20 | GSE222215 | 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: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:Kawasaki disease (KD) is the most common cause of acquired heart disease in children in developed countries. Based on single-cell RNA sequencing (scRNA-seq), we profiled peripheral blood mononuclear cells (PBMCs) from patients with acute KD before and after intravenous immunoglobulin (IVIG) therapy and from healthy controls. We identified the dynamics of cell abundance, gene expression patterns and biological processes underlying the immune dysregulation of each cell compartment. The single-cell landscape of both innate and adaptive immune responses provides new insights into pathogenesis and therapy of KD.
2021-03-12 | GSE168732 | GEO
Project description:blood plasma from children with kawasaki disease during illness and then ~1 year later (convalescent). blood plasma processed using Phree Kit (Phenomenox) and analyzed on a Vanquish-QExactive LC-MS system with HESI operated in positive and negative mode. Reverse phase LC was performed on a C18 column using a water - ACN gradient with 0.1% formic acid.
2019-01-31 | MSV000083388 | GNPS
Project description:Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers, the second leading cause of cancer mortality worldwide. Although HCC surgical treatment may be curative in the early stages, its five-year overall survival is only 50-70%. Advances in proteomic technologies have expanded the breadth and depth of cancer proteome characterization. Here, we present the largest characterization effort on proteomic profiling of 222 tumor and paired non-tumor tissues in clinically early HCC (Barcelona Clinic Liver Cancer (BCLC) stage 0 and A). Quantitative proteomic data identified three more-refined subtypes in the early- stage cohort of HCC (termed S-I, S-II and S-III) with different clinical outcomes. S-I retained hepatic detoxification and metabolic functions with the best prognosis, S-II increased molecular expression related to proliferation, and S-III showed distinct enrichment of tumor metastasis and immune response pathways and the poorest prognosis. The subtype specific signatures targeted by known FDA approved drugs or inhibitors under clinical investigations for HCC provide a novel resource for HCC therapeutic targets. A new mechanism of disrupted cholesterol homeostasis with aberrant accumulation of cholesteryl esters was also highlighted in S-III. Thus, this study represents the first proteomic stratification of early-stage HCC, providing insights into tumor biology and personalized targeted therapy.
2019-05-29 | PXD006512 | Pride