Endothelial cell response in Kawasaki disease and Multisystem Inflammatory Syndrome in Children
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ABSTRACT:
PROVIDER: PRJNA992502 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25204611_1.fastq.gz | Fastqsanger.gz | |||
| SRR25204611_2.fastq.gz | Fastqsanger.gz | |||
| SRR25204612_1.fastq.gz | Fastqsanger.gz | |||
| SRR25204612_2.fastq.gz | Fastqsanger.gz | |||
| SRR25204613_1.fastq.gz | Fastqsanger.gz |
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Project description:Abstract: Although Kawasaki disease (KD) and Multisystem inflammatory syndrome in children (MIS-C) share some clinical manifestations, their cardiovascular outcomes are different, and this may be reflected at the level of the endothelial cell (EC). We performed RNA-seq on cultured ECs incubated with pre-treatment sera from KD (n=5), MIS-C (n=7), and healthy controls (n=3). We conducted Weighted Gene Co-expression Network Analysis (WGCNA) using 935 transcripts differentially expressed between MIS-C and KD using soft filtering (un-adjusted p<0.05, >1.1 fold difference). We found seven gene modules annotated as increased TNFα/NFB pathway, decreased Endothelial-Mesenchymal Transition (EndoMT) and EC homeostasis, an-ti-inflammation and immune response, translation, and glucocorticoid responsive gene suppression in MIS-C. To further understand the difference in the EC response between KD and MIS-C, a hard filter was applied to identify 41 differentially expressed genes (DEGs) between KD and MIS-C (adjusted p<0.05, >2 fold-difference). Again, the majority was NFB pathway genes including nine upregulated pro-survival genes. Expression levels were higher in the genes influencing autophagy (UBD, EBI3, and SQSTM1). Other DEGs also supported the finding by WGCNA. Compared to KD, ECs in MIS-C had increased pro-survival transcripts, but reduced transcripts related to EndoMT and EC homeostasis. These differences in EC response may in-fluence the different cardiovascular outcomes in these two diseases.
2023-08-21 | GSE236833 | GEO
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: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:Multisystem inflammatory syndrome in Children (MIS-C) occurs in children between two and six weeks following an initial SARS-CoV-2 infection. The mechanism through which a minority of children develop the hyperinflammation characteristic of MIS-C, while others remain well, is unknown. In this study we present an in-depth assessment of the proteome of children before and after SARS-CoV-2 infection, including children with MIS-C. Reassuringly, these data show that there were minimal changes to the circulating proteome in healthy children as result of SARS-CoV2 infection and there was no evidence of continued inflammation following SARS-CoV-2 infection in children. However, activation of pro-inflammatory pathways and raised circulating markers of myocardial and vascular damage were found to be significantly associated with MIS-C. Our findings have been verified in silico using publicly available proteomic datasets and hence several promising candidate biomarker proteins for diagnosis of MIS-C are identified and described herein.
2025-08-25 | PXD051939 | Pride
Project description:In a subset of children and adolescents, SARS-CoV-2 infection leads to multisystem inflammatory syndrome in children (MIS-C), a severe hyperinflammatory shock occurring 4-8 weeks post-infection. MIS-C is characterized by a specific expansion of TCRVβ21.3+ T-cells and systemic hyperinflammation, with an unclear pathogenesis. Here, we show that acute MIS-C exhibits impaired reactivation of virus-specific memory T cells due to elevated TGF-β levels, mirroring severe COVID-19 in adults. Functionally, the impaired T-cell cytotoxicity is accompanied by TGF-β-response signatures and reduced antigen-presentation capabilities of monocytes, reversible by TGF-β blockade. MIS-C TCRVβ21.3+ T cells resemble Epstein-Barr Virus (EBV)-reactive T cells, displaying enhanced capability in eliminating EBV-infected B cells. Clinically, active MIS-C correlates with TGF-β-induced defects in T-cell cytotoxicity, elevated EBV seroprevalence, and EBV-reactivation. Our findings establish a connection between SARS-CoV-2 infection and COVID-19 sequelae in children, where reduced T-cell cytotoxicity induced by SARS-CoV-2-triggered TGF-β overproduction leads to EBV-reactivation and contributes to hyperinflammation.
2024-12-30 | GSE254179 | GEO
Project description:TGFβ links EBV to multisystem inflammatory syndrome in children
| PRJNA1068943 | ENA
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: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) 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:Although Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) share some clinical manifestations, their cardiovascular outcomes are different, and this may be reflected at the level of the endothelial cell (EC). We performed RNA-seq on cultured ECs incubated with pre-treatment sera from KD (n = 5), MIS-C (n = 7), and healthy controls (n = 3). We conducted a weighted gene co-expression network analysis (WGCNA) using 935 transcripts differentially expressed between MIS-C and KD using relaxed filtering (unadjusted p < 0.05, >1.1-fold difference). We found seven gene modules in MIS-C, annotated as an increased TNFα/NFκB pathway, decreased EC homeostasis, anti-inflammation and immune response, translation, and glucocorticoid responsive genes and endothelial-mesenchymal transition (EndoMT). To further understand the difference in the EC response between MIS-C and KD, stringent filtering was applied to identify 41 differentially expressed genes (DEGs) between MIS-C and KD (adjusted p < 0.05, >2-fold-difference). Again, in MIS-C, NFκB pathway genes, including nine pro-survival genes, were upregulated. The expression levels were higher in the genes influencing autophagy (UBD, EBI3, and SQSTM1). Other DEGs also supported the finding by WGCNA. Compared to KD, ECs in MIS-C had increased pro-survival transcripts but reduced transcripts related to EndoMT and EC homeostasis. These differences in the EC response may influence the different cardiovascular outcomes in these two diseases.
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