TY - JOUR
T1 - Sepsis pathogenesis and outcome are shaped by the balance between the transcriptional states of systemic inflammation and antimicrobial response
AU - Brandes-Leibovitz, Rachel
AU - Riza, Anca
AU - Yankovitz, Gal
AU - Pirvu, Andrei
AU - Dorobantu, Stefania
AU - Dragos, Adina
AU - Streata, Ioana
AU - Ricaño-Ponce, Isis
AU - de Nooijer, Aline
AU - Dumitrescu, Florentina
AU - Antonakos, Nikolaos
AU - Antoniadou, Eleni
AU - Dimopoulos, George
AU - Koutsodimitropoulos, Ioannis
AU - Kontopoulou, Theano
AU - Markopoulou, Dimitra
AU - Aimoniotou, Eleni
AU - Komnos, Apostolos
AU - Dalekos, George N.
AU - Ioana, Mihai
AU - Giamarellos-Bourboulis, Evangelos J.
AU - Gat-Viks, Irit
AU - Netea, Mihai G.
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/11/19
Y1 - 2024/11/19
N2 - Patients with sepsis differ in their clinical presentations and immune dysregulation in response to infection, but the fundamental processes that determine this heterogeneity remain elusive. Here, we aim to understand which types of immune dysregulation characterize patients with sepsis. To that end, we investigate sepsis pathogenesis in the context of two transcriptional states: one represents the immune response to eliminate pathogens (resistance, R) and the other is associated with systemic inflammation (SI). We find that patients with sepsis share a molecular fingerprint of a low R-to-SI balance—i.e., a low R relative to the level of SI. Differences between patients with sepsis are explained by the wide diversity of R and SI states that fall under this fingerprint, such as patients with high SI, patients with low R, or both. We show how this R/SI framework can be used to guide patient stratification that is relevant to disease prognosis and management, outperforming existing classifications of sepsis.
AB - Patients with sepsis differ in their clinical presentations and immune dysregulation in response to infection, but the fundamental processes that determine this heterogeneity remain elusive. Here, we aim to understand which types of immune dysregulation characterize patients with sepsis. To that end, we investigate sepsis pathogenesis in the context of two transcriptional states: one represents the immune response to eliminate pathogens (resistance, R) and the other is associated with systemic inflammation (SI). We find that patients with sepsis share a molecular fingerprint of a low R-to-SI balance—i.e., a low R relative to the level of SI. Differences between patients with sepsis are explained by the wide diversity of R and SI states that fall under this fingerprint, such as patients with high SI, patients with low R, or both. We show how this R/SI framework can be used to guide patient stratification that is relevant to disease prognosis and management, outperforming existing classifications of sepsis.
KW - immune response
KW - immunotheraphy
KW - infection
KW - patient stratification
KW - personalized medicine
KW - precision medicine
KW - sepsis
KW - septic shock
KW - systemic inflammation
UR - http://www.scopus.com/inward/record.url?scp=85209137915&partnerID=8YFLogxK
U2 - 10.1016/j.xcrm.2024.101829
DO - 10.1016/j.xcrm.2024.101829
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C2 - 39566468
AN - SCOPUS:85209137915
SN - 2666-3791
VL - 5
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 11
M1 - 101829
ER -