8b286c8e-96a6-4efd-af7a-275974caca1e - samples
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ABSTRACT:
PROVIDER: EGAD00001011134 | EGA |
REPOSITORIES: EGA
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Project description:To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki Disease (KD), bacterial infections and viral infections.
Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020-April 2021 were prospectively recruited. Whole blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C to those from children with KD, definite bacterial and viral infections. Data deposited here comprises samples from patients recruited into the DIAMONDS study.
| EGAS00001007409 | EGA
Project description:Multisystem inflammatory syndrome in children (MIS-C) occurs in some children approximately 2-6 weeks following infection with SARS-CoV-2. Clinical symptoms are highly overlapping with Kawasaki disease (KD) and bacterial (DB) and viral (DV) infections, making diagnosis particularly challenging. Host whole blood transcriptomics can reveal specific combinations of host genes whose expression patterns can distinguish between disease groups of interest. We performed whole blood RNA-Sequencing of individuals with MIS-C, KD, bacterial and viral infections to identify a number of host genes that, when combined, could be used to diagnose MIS-C. This data contains processed data only. Raw data will be available via a controlled access archive.
2023-06-27 | E-MTAB-12793 | biostudies-arrayexpress
Project description:Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), Multisystem Inflammatory Syndrome in Children (MIS-C), viral infections and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C — two conditions presenting with overlapping symptoms — with high performance (Test Area Under the Curve (AUC) = 0.97). We further extended this methodology into a multiclass machine learning framework that achieved 81% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes.
2024-09-11 | GSE255555 | GEO
Project description:Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children. Here, we define immune abnormalities in MIS-C compared to adult COVID-19 and pediatric/adult healthy controls using single-cell RNA sequencing, antigen receptor repertoire analysis, unbiased serum proteomics, and in vitro assays. Despite no evidence of active infection, we uncover elevated S100A-family alarmins in myeloid cells and marked enrichment of serum proteins that map to myeloid cells and pathways including cytokines, complement/coagulation, and fluid shear stress in MIS-C patients. Moreover, NK and CD8 T cell cytotoxicity genes are elevated, and plasmablasts harboring IgG1 and IgG3 are expanded. Consistently, we detect elevated binding of serum IgG from severe MIS-C patients to activated human cardiac microvascular endothelial cells in culture. Thus, we define immunopathology features of MIS-C with implications for predicting and managing this SARS-CoV2-induced critical illness in children.
2021-04-02 | GSE166489 | GEO
Project description:Multisystem Inflammatory Syndrome in Children (MIS-C) is a delayed-onset, COVID-19-related hyperinflammatory illness characterized by SARS-CoV-2 antigenemia, cytokine storm, and immune dysregulation. In severe COVID-19, neutrophil activation is central to hyperinflammatory complications, yet the role of neutrophils in MIS-C is undefined. Here, we collect blood from 152 children: 31 cases of MIS-C, 43 cases of acute pediatric COVID-19, and 78 pediatric controls. We find that MIS-C neutrophils display a granulocytic myeloid-derived suppressor cell (G-MDSC) signature with highly altered metabolism, distinct from the neutrophil interferon-stimulated gene (ISG) response we observe in pediatric COVID-19. Moreover, we observe extensive spontaneous neutrophil extracellular trap (NET) formation in MIS-C, and we identify neutrophil activation and degranulation signatures. Mechanistically, we determine that SARS-CoV-2 immune complexes are sufficient to trigger NETosis. Our findings suggest that the hyperinflammatory presentation during MIS-C could be mechanistically linked to persistent SARS-CoV-2 antigenemia, driven by uncontrolled neutrophil activation and NET release in the vasculature.
2022-11-05 | GSE217370 | GEO
Project description:In order to understand the immunopathogenesis of severe influenza H1N1/09, we compared the whole blood RNA transcriptome of children hospitalised with H1N1/09 infection with that of children hospitalised with RSV or bacterial infection Blood was collected into PAX gene tubes (PreAnalytiX). Total RNA integrity was assessed using an Agilent 2100 Bioanalyzer (Agilent, Palo Alto, CA). Labeled cRNA was hybridized to Illumina Human HT-12 v3 Beadchips. Observational, prospective study. Patients were recruited at or after presentation to hospital. Main inclusion criteria were presence of illness of sufficient severity to warrant blood tests for clinical reasons, in child aged <17 years. Patient numbers recruited were as follows: H1N1/09 infection (n=25) RSV (n=34) (n=21), and healthy paediatric controls (n=33). After exclusion of children with co-infections, numbers of arrays analysed in were as follows: H1N1/09 n=19; RSV n=22; bacterial infection n=18; controls n=33
2013-09-05 | E-GEOD-42026 | biostudies-arrayexpress
Project description:While fewer cases of severe Coronavirus Disease 2019 (COVID-19) are reported globally in children, a small proportion of SARS-CoV-2 infected children develop a novel pediatric febrile entity called multisystem inflammatory syndrome in children (MIS-C) that develops 2 to 5 weeks after initial SARS-CoV-2 exposure. MIS-C primarily effects male children and children of Hispanic or black descent. MIS-C manifests as a severe and uncontrolled inflammatory response with multiorgan involvement. A hyperinflammatory state is evidenced by clinical makers of inflammation including high levels of C-reactive protein (CRP), ferritin, and D-dimers, and an increased expression of pro-inflammatory cytokines. Children often present with persistent fever, severe gastrointestinal symptoms, cardiovascular manifestations, respiratory symptoms and neurological symptoms6-11,13. Cardiovascular manifestations include hypotension, shock, cardiac dysfunction, myocarditis and pericardial effusion. In the united states, admission to the intensive care unit occurs in approximately 58% of cases. To understand disease pathogenesis of MIS-C and proteins associated with the severe form of disease we performed proteomics analysis of serum or plasma samples. We collected serum from healthy children (SARS-CoV-2 negative, n=20), mild MIS-C (non-ICU, n=5) and severe MIS-C (ICU, n = 20) patients. MIS-C definition and diagnosis was performed according to CDC guidelines. Healthy adult serum (n = 4) was also used for reference ranges quality control and we obtained plasma samples from Kawasaki Disease (KD; n=7) patients that were recruited before the Coronavirus Disease 2019 (COVID-19) pandemic.
2021-09-29 | PXD025462 | Pride
Project description:The pathologic mechanisms causing Multisystem 38 Inflammatory Syndrome in Children (MIS-C) are not yet known; we sought to use high throughput proteomics to uncover signatures of dysregulation suggestive of pathophysiology fo this condition. MIS-C is a major complication of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic in pediatric patients. Weeks after an often mild or asymptomatic initial infection with SARS-CoV-2 children may present with a severe shock-like picture and marked inflammation. Children with MIS-C present with varying degrees of cardiovascular and hyperinflammatory symptoms. We performed a comprehensive analysis of more than 1400 proteins in the plasma proteome of children with SARS-CoV-2 and MIS-C.
2021-11-25 | PXD029375 | Pride
Project description:Pneumonia stands as the primary cause of death among children under five, with its onset attributed to a broad spectrum of microorganisms. Diagnosis poses an ongoing challenge, relying on clinical or microbiological criteria, often resulting in delayed and inaccurate treatment and unnecessary therapy. Our research focuses on identifying host transcriptomic biomarkers in the blood of children affected by viral and bacterial pneumonia, alongside healthy controls. The main goal is to establish a gene-expression signature enhancing disease diagnosis and management. We conducted an analysis of a total of 192 whole blood samples, comprising 38 controls and 154 viral and bacterial pneumonia patients recruited through the EUCLIDS clinical network. Our investigation identified 5,486 differentially expressed genes (DEGs) when comparing blood RNA from pneumonia patients with healthy controls. Functional enrichment analysis highlighted pathways related to the immune system response, encompassing neutrophil degranulation, humoral immune response, and various inflammatory pathways. In the comparative analysis of gene expression between viral and bacterial pneumonia patients, we identified 272 DEGs. Gene set analysis revealed a significant difference in pathway enrichment for the immune response, contingent on the over-regulation of gene sets in viral or bacterial pneumonias. Furthermore, we identified a 5-transcript host signature specifically designed to distinguish between viral and bacterial pediatric pneumonia (FAM20A, BAG3, TDRD9, MXRA7 and KLF14; AUC: 0.95 [0.88–1.00]), pseudo-validated in a cohort including probable bacterial and viral patients (AUC: 0.87 [0.77–0.97]). This signature holds the potential to enhance the accuracy of previously described general transcript-based signatures for viral and bacterial infections.
2024-12-09 | GSE261482 | GEO
Project description:A significant surge in cases of multisystem inflammatory syndrome in children (MIS-C, also called Pediatric Inflammatory Multisystem Syndrome - PIMS) has been observed amidst the COVID-19 pandemic. MIS-C shares many clinical features with Kawasaki disease (KD), although clinical course and outcomes are divergent. We analyzed whole blood RNA sequences, serum cytokines, and formalin fixed heart tissues from these patients using a computational toolbox of two gene signatures, i.e., viral pandemic (ViP), and a subset of it called, severe (s)ViP signatures that were developed in the context of SARS-CoV-2 infection in COVID-19 and a 13-transcript signature previously demonstrated to be diagnostic for KD. Our analyses revealed that KD and MIS-C are on the same continuum of the host immune response as COVID-19 but diverge with two different cardiac phenotypes. The ViP signatures helped unravel the nature of the host immune response (IL15-centric) in MIS-C and KD, reveal unique targetable cytokine pathways in MIS-C, place MIS-C farther along in the spectrum in severity compared to KD and pinpoint key clinical (reduced cardiac function) and laboratory (thrombocytopenia and eosinopenia) parameters that can be useful to track severity.
2022-03-20 | GSE178491 | GEO