Identifying immune signatures of sepsis in very preterm babies
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA989030 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25068800_1.fastq.gz | Fastqsanger.gz | |||
| SRR25068800_2.fastq.gz | Fastqsanger.gz | |||
| SRR25068801_1.fastq.gz | Fastqsanger.gz | |||
| SRR25068801_2.fastq.gz | Fastqsanger.gz | |||
| SRR25068790.fastq.gz | Fastqsanger.gz |
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Project description:Bacterial infections are a major cause of mortality in preterm babies, yet our understanding of early-life disease-associated immune dysregulation remains limited. Here, we combined multi-parameter flow cytometry, single-cell RNA sequencing (scRNAseq) and targeted plasma analysis to prospectively and longitudinally profile blood from very preterm babies (<32 weeks gestation) across episodes of invasive bacterial infection (sepsis). We identified a dynamically changing peripheral blood immune signature of sepsis, including lymphopenia, reduced dendritic cell frequencies and monocyte HLA-DR expression, which characterized sepsis even when the common clinical marker of inflammation, C-reactive protein (CRP) was not elevated. Furthermore, scRNAseq showed upregulation of amphiregulin in different leukocyte populations during sepsis, which we validated as a plasma analyte that correlated with clinical signs of disease, even when CRP was normal. This study provides new insights into immune pathways associated with early-life sepsis and identifies potential immune analytes as diagnostic adjuncts for sepsis to guide targeted antibiotic prescribing.
2023-11-23 | GSE236099 | GEO
Project description:Host immune responses during late-onset sepsis (LOS) in very preterm infants are poorly characterised due to a complex and dynamic pathophysiology and challenges in working with small available blood volumes. We present here an unbiased transcriptomic analysis of whole peripheral blood from very preterm infants at the time of LOS. RNA-Seq was performed on peripheral blood samples (6 – 29 days postnatal age) taken at the time of suspected LOS from very preterm infants <30 weeks gestational age. Infants were classified based on blood culture positivity and elevated C-reactive protein concentrations as having confirmed LOS (n=5), possible LOS (n=4) or no LOS (n=9). Bioinformatics and statistical analyses performed included pathway over-representation and protein-protein interaction network analyses. Plasma cytokine immunoassays were performed to validate differentially expressed cytokine pathways.The blood leukocyte transcriptional responses of infants with confirmed LOS differed significantly from infants without LOS (1,317 differentially expressed genes). However, infants with possible LOS could not be distinguished from infants with no LOS or confirmed LOS. Transcriptional alterations associated with LOS included genes involved in pathogen recognition (mainly TLR pathways), cytokine signalling (both pro-inflammatory and inhibitory responses), immune and haematological regulation (including cell death pathways), and metabolism (altered cholesterol biosynthesis). At the transcriptional-level cytokine responses during LOS were characterised by over-representation of IFN-α/β, IFN-γ, IL-1 and IL-6 signalling pathways and up-regulation of genes for inflammatory responses. Infants with confirmed LOS had significantly higher levels of IL-1α and IL-6 in their plasma. Blood responses in very preterm infants with LOS are characterised by altered host immune responses that appear to reflect unbalanced immuno-metabolic homeostasis.
2020-06-03 | GSE138712 | GEO
Project description:Bacterial sepsis is associated with high morbidity and mortality in preterm infants. However, diagnosis of sepsis and identification of the causative agent remains challenging. Our aim was to determine genome-wide expression profiles of very low birth weight (VLBW) infants with and without bacterial sepsis and assess differences.
2016-05-29 | E-MTAB-4785 | biostudies-arrayexpress
Project description:Whole blood transcriptional responses of very preterm infants during late-onset sepsis
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Project description:Here, we investigated γδ T cells in a longitudinal cohort of preterm neonates during the first year of life. Our data reveal dynamic postnatal maturation patterns of γδ T cell subsets, which are largely age-dependent. We report on the expansion of fetal-derived γδ T cells in preterm neonates with sepsis. Single cell transcriptome analyses identified HLA-DRhigh and CD83+ γδ T cells in neonatal sepsis.
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Project description:Meconium microbiome of very preterm infants across Germany
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Project description:Neonates manifest a unique host response to sepsis even among other children. Preterm neonates may experience sepsis soon after birth or during often protracted birth hospitalizations as they attain physiologic maturity. We examined the transcriptome using genome-wide expression profiling on prospectively collected peripheral blood samples from infants evaluated for sepsis within 24 hours after clinical presentation. Simultaneous plasma samples were examined for alterations in inflammatory mediators. Group designation (sepsis or uninfected) was determined retrospectively based on clinical exam and laboratory results over the next 72 hours from the time of evaluation. Unsupervised analysis showed the major node of separation between groups was timing of sepsis episode relative to birth (early, <3 days or late, >3 days). Principal component analyses revealed significant differences between patients with early or late sepsis despite the presence of similar key immunologic pathway aberrations in both groups. Unique to neonates, the uninfected state and host response to sepsis is significantly affected by timing relative to birth. Future therapeutic approaches may need to be tailored to the timing of the infectious event based on post-natal age. We used human microarrays to detail the molecular profile of the events that occur following sepsis in hospitalized neonates Please note that 'uninfected chorio' represents babies who were not infected but had chorioamnionitis exposure
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Project description:Preterm birth is a major cause of infant mortality and morbidity. The rate of preterm birth is 5-9% in most developed countries and 12% in the United States with approximately 15 million children born prematurely each year. Globally, prematurity is the second most common cause of death in children under the age of five years. To characterize the transcriptomic changes between preterm and full term neonates, RNA-sequencing was applied altogether to 14 cord blood samples. The analysis of the RNA-sequencing data revealed that the spontaneous preterm delivery resulted in systemic inflammatory responses at the gene and pathway level in the fetus.
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Project description:DNA methylation is the current strategy in the field of biomarker discovery due to its prognostic efficiency. Its role in prognosis and early diagnosis has been recognized in various types of cancer. Sepsis still remains one of the major causes of neonatal mortality due to the lack of sensitive diagnostic and prognostic biomarkers. Delay in sepsis diagnosis leads to treatment difficulties and poor outcomes. In this study, we have done an epigenome wide search to identify potential markers for prognosis of neonatal sepsis which may improve the treatment strategies. Illumina 450K methylation microarray revealed that the genes involved in transendothelial leukocyte migration were differentially methylated in septic newborns compared to non-septic newborns, especially the Protocadherin Beta group. Genes like ITGB2-AS1, CCS were found to be differentially methylated significantly, which gives the hope of developing novel, potential epigenetic markers for neonatal sepsis. From this study, we conclude that DNA methylation might play crucial functions in the pathophysiology of neonatal sepsis which was obvious from the difference in methylation level among septic and non-septic babies. In future, the potentiality of these epigenetic biomarkers can be studied in large scale with appropriate techniques which will give further in depth knowledge in this context. DNA methylation analysis of three septic newborns and three non-septic newborns were performed with Illumina Infinium HumanMethylation450 BeadChip. Peripheral venous blood sample was collected from the babies during the third day of birth while taking blood for routine investigations. Non-septic babies are babies admitted to NICU and sampled for other minor ailments. Genomic DNA was extracted using QIAmp DNA Blood Mini kit (Qiagen, Hilden, Germany) and bisulfite treated using EZ DNA methylation kit (Zymoresearch, USA).
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Project description:To investigate if appropriately adjusted parenteral glucose supply may help to shift liver metabolism profiling to further prevent sepsis or improve sepsis outcomes of preterm newborns, we using a preterm pig model inoculated with Staphylococcus epidermidis to mimic the inflammation condition of preterm newborns at birth and treated them with different parenteral nutrition glucose supplyment. We then performed gene expression profiling analysis using data obtained from RNA-seq of preterm pigs` liver tissue, which collected at 22 hours after SE infection, treated with different parenteral glucose supply.
2022-06-29 | GSE201550 | GEO