Validating the genomic signature of pediatric septic shock

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Accordingly, novel therapeutic strategies for septic shock are now being contemplated with a focus on restoration of the adaptive immune system, rather than inhibition of the innate immune system and the inflammatory response (23,24).

A variety of clinical and experimental data indicate that developmental age influences the immune system and hence the host response to sepsis (4,25,26,27,28).

The subclass-defining gene signature was subsequently distilled to the top 100 class predictor genes, and these genes corresponded to T-cell receptor signaling, B-cell receptor signaling, glucocorticoid-receptor signaling, and peroxisome proliferator–activated receptor-α activation (30).The studies have progressed from an initial discovery-oriented and exploratory phase to a new phase in which the data are being translated and applied to address several areas of clinical need.The expression data are based on whole blood–derived RNA and are focused on the initial, acute presentation to the pediatric intensive care unit (PICU) with a clinical diagnosis of septic shock.This pattern of gene repression is evident within the first 24 h of presentation to the pediatric intensive care unit (PICU) with septic shock and persists at least into the third day of PICU admission.Analogous studies in adults with septic shock, and in adults suffering from major traumatic injuries, have also demonstrated similar patterns of gene repression corresponding to the adaptive immune system (18,19,20,21,22).

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