TY - JOUR
T1 - International multi-cohort analysis identifies novel framework for quantifying immune dysregulation in critical illness
T2 - results of the SUBSPACE consortium
AU - Moore, Andrew R
AU - Zheng, Hong
AU - Ganesan, Ananthakrishnan
AU - Hasin-Brumshtein, Yehudit
AU - Maddali, Manoj V
AU - Levitt, Joseph E
AU - van der Poll, Tom
AU - Scicluna, Brendon P
AU - Giamarellos-Bourboulis, Evangelos J
AU - Kotsaki, Antigone
AU - Martin-Loeches, Ignacio
AU - Garduno, Alexis
AU - Rothman, Richard E
AU - Sevransky, Jonathan
AU - Wright, David W
AU - Atreya, Mihir R
AU - Moldawer, Lyle L
AU - Efron, Philip A
AU - Marcela, Kralovcova
AU - Karvunidis, Thomas
AU - Giannini, Heather M
AU - Meyer, Nuala J
AU - Sweeney, Timothy E
AU - Rogers, Angela J
AU - Khatri, Purvesh
PY - 2024/11/15
Y1 - 2024/11/15
N2 - Progress in the management of critical care syndromes such as sepsis, Acute Respiratory Distress Syndrome (ARDS), and trauma has slowed over the last two decades, limited by the inherent heterogeneity within syndromic illnesses. Numerous immune endotypes have been proposed in sepsis and critical care, however the overlap of the endotypes is unclear, limiting clinical translation. The SUBSPACE consortium is an international consortium that aims to advance precision medicine through the sharing of transcriptomic data. By evaluating the overlap of existing immune endotypes in sepsis across over 6,000 samples, we developed cell-type specific signatures to quantify dysregulation in these immune compartments. Myeloid and lymphoid dysregulation were associated with disease severity and mortality across all cohorts. This dysregulation was not only observed in sepsis but also in ARDS, trauma, and burn patients, indicating a conserved mechanism across various critical illness syndromes. Moreover, analysis of randomized controlled trial data revealed that myeloid and lymphoid dysregulation is linked to differential mortality in patients treated with anakinra or corticosteroids, underscoring its prognostic and therapeutic significance. In conclusion, this novel immunology-based framework for quantifying cellular compartment dysregulation offers a valuable tool for prognosis and therapeutic decision-making in critical illness.
AB - Progress in the management of critical care syndromes such as sepsis, Acute Respiratory Distress Syndrome (ARDS), and trauma has slowed over the last two decades, limited by the inherent heterogeneity within syndromic illnesses. Numerous immune endotypes have been proposed in sepsis and critical care, however the overlap of the endotypes is unclear, limiting clinical translation. The SUBSPACE consortium is an international consortium that aims to advance precision medicine through the sharing of transcriptomic data. By evaluating the overlap of existing immune endotypes in sepsis across over 6,000 samples, we developed cell-type specific signatures to quantify dysregulation in these immune compartments. Myeloid and lymphoid dysregulation were associated with disease severity and mortality across all cohorts. This dysregulation was not only observed in sepsis but also in ARDS, trauma, and burn patients, indicating a conserved mechanism across various critical illness syndromes. Moreover, analysis of randomized controlled trial data revealed that myeloid and lymphoid dysregulation is linked to differential mortality in patients treated with anakinra or corticosteroids, underscoring its prognostic and therapeutic significance. In conclusion, this novel immunology-based framework for quantifying cellular compartment dysregulation offers a valuable tool for prognosis and therapeutic decision-making in critical illness.
U2 - 10.1101/2024.11.12.623298
DO - 10.1101/2024.11.12.623298
M3 - Article
C2 - 39605502
SN - 2692-8205
JO - bioRxiv : the preprint server for biology
JF - bioRxiv : the preprint server for biology
ER -