Gene Expression Scoring of Immune Activity Levels for Precision Use of Hydrocortisone in Vasodilatory Shock. Issue 3 (March 2022)

• Record Type: Journal Article
• Authors: Yao, Lijing; Rey, Diego Ariel; Bulgarelli, Lucas; Kast, Rachel; Osborn, Jeff; Van Ark, Emily; Fang, Li Tai; Lau, Bayo; Lam, Hugo; Teixeira, Leonardo Maestri; Neto, Ary Serpa; Bellomo, Rinaldo; Deliberato, Rodrigo Octávio
• Is Part Of: Shock. Volume 57:Issue 3(2022)
• Publication Date: 2022-03
• Subjects: Gene-expression score -- personalized medicine -- shock -- Abbreviations -- APACHE -- Acute Physiology and Chronic Health Evaluation -- AUROC -- Area Under the Receiver Operator Characteristic Curve -- Burn trial -- Low-dose hydrocortisone reduces norepinephrine duration in severe burn patients a randomized clinical trial -- DEGs -- Differentially Expressed Genes -- FDA -- Food and Drug Administration -- GEO -- Gene Expression Omnibus -- GO -- Gene Ontology -- IA -- Immune-adaptive -- IA-P -- immune-adaptive prevalent -- IC -- Immune-coagulant -- ICU -- Intensive Care Unit -- IN -- Immune-innate -- IN-P -- immune-innate prevalent -- IRB -- Institutional Review Board -- MAD -- Median Absolute Deviation -- PAM -- Partition Around Medoids -- SOFA -- Sequential Organ Failure Assessment -- VANISH -- Vasopressin vs Norepinephrine as Initial Therapy in Septic Shock; Shock -- Periodicals; Shock -- Periodicals; Choc (Pathologie) -- Périodiques; Shock; Periodicals; 616.0475
• DOI: 10.1097/SHK.0000000000001910
• Languages: English
• ISSNs: 1073-2322

Abstract

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.