Pediatric critical illness endotypes reveal distinct outcomes and immune pathways shared across cause of illness
Abstract
Characterization 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 higher proportions of naive and resting memory CD4 T cells, lower proportions of neutrophils, and reduced expression of gene sets associated with tumor necrosis factor alpha (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.
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BibTeX
@article{carter2026pediatric,
title = {{Pediatric critical illness endotypes reveal distinct outcomes and immune pathways shared across cause of illness}},
author = {Michael Carter and Joshua Hageman and Yael Feinstein and Jethro Herberg and Dominic Habgood-Coote and Victoria Wright and Samuel Nichols and Nazima Pathan and Naomi Edmonds and Philip Cowie and Katie Burnham and Alexander Mentzer and Julian Knight and Michael Levin and Myrsini Kaforou and Simon Nadel and Mark Peters and Padmanabhan Ramnarayan},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2025.114210},
url = {https://hal.science/hal-05795849v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Pediatric critical illness endotypes reveal distinct outcomes and immune pathways shared across cause of illness
AU - Michael Carter
AU - Joshua Hageman
AU - Yael Feinstein
AU - Jethro Herberg
AU - Dominic Habgood-Coote
AU - Victoria Wright
AU - Samuel Nichols
AU - Nazima Pathan
AU - Naomi Edmonds
AU - Philip Cowie
AU - Katie Burnham
AU - Alexander Mentzer
AU - Julian Knight
AU - Michael Levin
AU - Myrsini Kaforou
AU - Simon Nadel
AU - Mark Peters
AU - Padmanabhan Ramnarayan
PY - 2026
DA - 2026/10/12
JO - iScience
DO - 10.1016/j.isci.2025.114210
UR - https://hal.science/hal-05795849v1
AB - Characterization 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 higher proportions of naive and resting memory CD4 T cells, lower proportions of neutrophils, and reduced expression of gene sets associated with tumor necrosis factor alpha (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.
SN - 2589-0042
ER -