1. Gene Expression Scoring of Immune Activity Levels for Precision Use of Hydrocortisone in Vasodilatory Shock.
- Author
-
Yao L, Rey DA, Bulgarelli L, Kast R, Osborn J, Van Ark E, Fang LT, Lau B, Lam H, Teixeira LM, Neto AS, Bellomo R, and Deliberato RO
- Subjects
- Aged, Female, Humans, Male, Middle Aged, Precision Medicine, Retrospective Studies, Shock genetics, Anti-Inflammatory Agents therapeutic use, Gene Expression physiology, Hydrocortisone therapeutic use, Immunity genetics, Shock drug therapy, Shock immunology
- Abstract
Purpose: Among patients with vasodilatory shock, gene expression scores may identify different immune states. We aimed to test whether such scores are robust in identifying patients' immune state and predicting response to hydrocortisone treatment in vasodilatory shock., Materials and Methods: We selected genes to generate continuous scores to define previously established subclasses of sepsis. We used these scores to identify a patient's immune state. We evaluated the potential for these states to assess the differential effect of hydrocortisone in two randomized clinical trials of hydrocortisone versus placebo in vasodilatory shock., Results: We initially identified genes associated with immune-adaptive, immune-innate, immune-coagulant functions. From these genes, 15 were most relevant to generate expression scores related to each of the functions. These scores were used to identify patients as immune-adaptive prevalent (IA-P) and immune-innate prevalent (IN-P). In IA-P patients, hydrocortisone therapy increased 28-day mortality in both trials (43.3% vs 14.7%, P = 0.028) and (57.1% vs 0.0%, P = 0.99). In IN-P patients, this effect was numerically reversed., Conclusions: Gene expression scores identified the immune state of vasodilatory shock patients, one of which (IA-P) identified those who may be harmed by hydrocortisone. Gene expression scores may help advance the field of personalized medicine., Competing Interests: ROD, LY, RK, EVA, LB, JO, LTF, and DAR are employees of Endpoint Health, Inc. BL and Hl are employees of HypaHub, Inc. ASN reported receiving personal fees from Dräger unrelated to the submitted work and consulting fees from Endpoint Health. RB has no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)
- Published
- 2022
- Full Text
- View/download PDF