Identifying immune signatures of sepsis to increase diagnostic accuracy in very preterm babies.
Abhishek DasG AriyakumarN GuptaS KamdarAdele BarugahareD Deveson-LucasS GeeK CosteloeMartin S DaveyP FlemingDeena L GibbonsPublished in: Nature communications (2024)
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 combine multi-parameter flow cytometry, single-cell RNA sequencing and plasma analysis to longitudinally profile blood from very preterm babies (<32 weeks gestation) across episodes of invasive bacterial infection (sepsis). We identify a dynamically changing blood immune signature of sepsis, including lymphopenia, reduced dendritic cell frequencies and myeloid cell HLA-DR expression, which characterizes sepsis even when the common clinical marker of inflammation, C-reactive protein, is not elevated. Furthermore, single-cell RNA sequencing identifies upregulation of amphiregulin in leukocyte populations during sepsis, which we validate as a plasma analyte that correlates with clinical signs of disease, even when C-reactive protein is normal. This study provides insights into immune pathways associated with early-life sepsis and identifies immune analytes as potential diagnostic adjuncts to standard tests to guide targeted antibiotic prescribing.
Keyphrases
- single cell
- early life
- gestational age
- septic shock
- acute kidney injury
- intensive care unit
- rna seq
- dendritic cells
- flow cytometry
- preterm birth
- poor prognosis
- genome wide
- high throughput
- low birth weight
- cell proliferation
- oxidative stress
- gene expression
- regulatory t cells
- coronary artery disease
- bone marrow
- stem cells
- cardiovascular events
- mesenchymal stem cells
- editorial comment
- genetic diversity