Journal article
Identification of a transcriptome profile associated with improvement of organ function in septic shock patients after early supportive therapy.
- Barcella M Dipartimento di Scienze della Salute, Università degli Studi di Milano, Via Rudini 8, 20142, Milan, Italy.
- Bollen Pinto B Department of Anaesthesia, Pharmacology and Intensive Care, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, Geneva, 1205, Switzerland.
- Braga D Dipartimento di Scienze della Salute, Università degli Studi di Milano, Via Rudini 8, 20142, Milan, Italy.
- D'Avila F Dipartimento di Scienze della Salute, Università degli Studi di Milano, Via Rudini 8, 20142, Milan, Italy.
- Tagliaferri F Dipartimento di Scienze della Salute, Università degli Studi di Milano, Via Rudini 8, 20142, Milan, Italy.
- Cazalis MA Laboratoire Commun de Recherche HCL-bioMérieux, Hôpital Edouard Herriot, 376 Chemin de l'Orme, 6928 Marcy-l'Etoile, Lyon, France.
- Monneret G Hospices Civils de Lyon, Hôpital Edouard Herriot, Laboratoire d'Immunologie, 5 Place d'Arsonval, 69437, Lyon cedex 03, France.
- Herpain A Department of Intensive Care, Hospital Erasme, Hospital, Université Libre de Bruxelles, Route de Lennik 808, Brussels, 1070, Belgium.
- Bendjelid K Department of Anaesthesia, Pharmacology and Intensive Care, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, Geneva, 1205, Switzerland.
- Barlassina C Dipartimento di Scienze della Salute, Università degli Studi di Milano, Via Rudini 8, 20142, Milan, Italy. cristina.barlassina@unimi.it.
- 2018-11-23
Published in:
- Critical care (London, England). - 2018
Critical illness
Gene expression
RNA-Seq
SOFA score
Septic shock
APACHE
Adult
Aged
Aged, 80 and over
Belgium
Female
Humans
Intensive Care Units
Male
Middle Aged
Organ Dysfunction Scores
Shock, Septic
Statistics, Nonparametric
Switzerland
Transcriptome
English
BACKGROUND
Septic shock is the most severe complication of sepsis and this syndrome is associated with high mortality. Treatment of septic shock remains largely supportive of hemodynamics and tissue perfusion. Early changes in organ function assessed by the Sequential Organ Function Assessment (SOFA) score are highly predictive of the outcome. However, the individual patient's response to supportive therapy is very heterogeneous, and the mechanisms underlying this variable response remain elusive. The aim of the study was to investigate the transcriptome of whole blood in septic shock patients with different responses to early supportive hemodynamic therapy assessed by changes in SOFA scores within the first 48 h from intensive care unit (ICU) admission.
METHODS
We performed whole blood RNA sequencing in 31 patients: 17 classified as responders (R) and 14 as non-responders (NR). Gene expression was investigated at ICU admission (time point 1, or T1), comparing R with NR [padj < 0.01; Benjamini-Hochberg (BH)] and over time from T1 to T2 (48 h later) in R and NR independently (paired analysis, padj < 0.01; BH). Then the differences in gene expression trends over time were evaluated (Mann-Whitney, P <0.01). To identify enriched biological processes, we performed an over-representation analysis based on a right-sided hypergeometric test with Bonferroni step-down as multiple testing correction (padj < 0.05).
RESULTS
At ICU admission, we did not identify differentially expressed genes (DEGs) between the two groups. In the transition from T1 to T2, the activation of genes involved in T cell-mediated immunity, granulocyte and natural killer (NK) cell functions, and pathogen lipid clearance was noted in the R group. Genes involved in acute inflammation were downregulated in both groups.
CONCLUSIONS
Within the limits of a small sample size, our results could suggest that early activation of genes of the adaptive immune response is associated with an improvement in organ function.
Septic shock is the most severe complication of sepsis and this syndrome is associated with high mortality. Treatment of septic shock remains largely supportive of hemodynamics and tissue perfusion. Early changes in organ function assessed by the Sequential Organ Function Assessment (SOFA) score are highly predictive of the outcome. However, the individual patient's response to supportive therapy is very heterogeneous, and the mechanisms underlying this variable response remain elusive. The aim of the study was to investigate the transcriptome of whole blood in septic shock patients with different responses to early supportive hemodynamic therapy assessed by changes in SOFA scores within the first 48 h from intensive care unit (ICU) admission.
METHODS
We performed whole blood RNA sequencing in 31 patients: 17 classified as responders (R) and 14 as non-responders (NR). Gene expression was investigated at ICU admission (time point 1, or T1), comparing R with NR [padj < 0.01; Benjamini-Hochberg (BH)] and over time from T1 to T2 (48 h later) in R and NR independently (paired analysis, padj < 0.01; BH). Then the differences in gene expression trends over time were evaluated (Mann-Whitney, P <0.01). To identify enriched biological processes, we performed an over-representation analysis based on a right-sided hypergeometric test with Bonferroni step-down as multiple testing correction (padj < 0.05).
RESULTS
At ICU admission, we did not identify differentially expressed genes (DEGs) between the two groups. In the transition from T1 to T2, the activation of genes involved in T cell-mediated immunity, granulocyte and natural killer (NK) cell functions, and pathogen lipid clearance was noted in the R group. Genes involved in acute inflammation were downregulated in both groups.
CONCLUSIONS
Within the limits of a small sample size, our results could suggest that early activation of genes of the adaptive immune response is associated with an improvement in organ function.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1186/s13054-018-2242-3
- PMID 30463588
- Persistent URL
- https://sonar.ch/global/documents/232867
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