Pediatric critical illness endotypes reveal distinct outcomes and immune pathways shared across cause of illness
File(s)
Article in press
Author(s)
Type
Journal Article
Abstract
Characterisation of shared patterns of immune responses in critical illnesses, known as “endotypes”, may have therapeutic significance. Using unsupervised k-means clustering of genome-wide gene expression profiling, we derived, validated and assigned endotype membership in 382 children with diverse critical illnesses recruited to the BASIC study. We identified two robust endotypes, BASIC endotype 1 (122, 31.9%, children), and BASIC endotype 2 (260, 68.1%, children), present in children with diverse illnesses and age groups. BASIC endotype 1 membership was associated with 4.1 days of increased duration of mechanical ventilation and a non-significant association with mortality. BASIC endotype 1 membership was associated with increase naïve and resting memory CD4 T cell proportions, lower neutrophil proportions and lower gene expression sets associated with tumour necrosis factor (TNF)-α, interferon-γ, interferon-α, and interleukin-6/JAK/STAT pathways in comparison with BASIC endotype 2. These BASIC endotypes may enable stratified trials of treatment for immune dysfunction.
Date Issued
2025-11-26
Date Acceptance
2025-11-20
Citation
iScience, 2025
ISSN
2589-0042
Publisher
Elsevier
Journal / Book Title
iScience
Copyright Statement
© 2025 Published by Elsevier Inc. Licensed under a Creative Commons Attribution (CC BY 4.0)
License URL
Identifier
10.1016/j.isci.2025.114210
Publication Status
Published online
Article Number
ARTN 114210
Date Publish Online
2025-11-26