Identification of a transcriptome profile associated with improvement of organ function in septic shock patients after early supportive therapy
Abstract 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 Assessm...
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doaj-522bc29032614c9e9f68ead591ab10132020-11-25T01:33:56ZengBMCCritical Care1364-85352018-11-0122111310.1186/s13054-018-2242-3Identification of a transcriptome profile associated with improvement of organ function in septic shock patients after early supportive therapyMatteo Barcella0Bernardo Bollen Pinto1Daniele Braga2Francesca D’Avila3Federico Tagliaferri4Marie-Angelique Cazalis5Guillaume Monneret6Antoine Herpain7Karim Bendjelid8Cristina Barlassina9Dipartimento di Scienze della Salute, Università degli Studi di MilanoDepartment of Anaesthesia, Pharmacology and Intensive Care, Geneva University HospitalsDipartimento di Scienze della Salute, Università degli Studi di MilanoDipartimento di Scienze della Salute, Università degli Studi di MilanoDipartimento di Scienze della Salute, Università degli Studi di MilanoLaboratoire Commun de Recherche HCL-bioMérieux, Hôpital Edouard HerriotHospices Civils de Lyon, Hôpital Edouard Herriot, Laboratoire d’ImmunologieDepartment of Intensive Care, Hospital Erasme, Hospital, Université Libre de BruxellesDepartment of Anaesthesia, Pharmacology and Intensive Care, Geneva University HospitalsDipartimento di Scienze della Salute, Università degli Studi di MilanoAbstract 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.http://link.springer.com/article/10.1186/s13054-018-2242-3Critical illnessSOFA scoreGene expressionRNA-SeqSeptic shock |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matteo Barcella Bernardo Bollen Pinto Daniele Braga Francesca D’Avila Federico Tagliaferri Marie-Angelique Cazalis Guillaume Monneret Antoine Herpain Karim Bendjelid Cristina Barlassina |
spellingShingle |
Matteo Barcella Bernardo Bollen Pinto Daniele Braga Francesca D’Avila Federico Tagliaferri Marie-Angelique Cazalis Guillaume Monneret Antoine Herpain Karim Bendjelid Cristina Barlassina Identification of a transcriptome profile associated with improvement of organ function in septic shock patients after early supportive therapy Critical Care Critical illness SOFA score Gene expression RNA-Seq Septic shock |
author_facet |
Matteo Barcella Bernardo Bollen Pinto Daniele Braga Francesca D’Avila Federico Tagliaferri Marie-Angelique Cazalis Guillaume Monneret Antoine Herpain Karim Bendjelid Cristina Barlassina |
author_sort |
Matteo Barcella |
title |
Identification of a transcriptome profile associated with improvement of organ function in septic shock patients after early supportive therapy |
title_short |
Identification of a transcriptome profile associated with improvement of organ function in septic shock patients after early supportive therapy |
title_full |
Identification of a transcriptome profile associated with improvement of organ function in septic shock patients after early supportive therapy |
title_fullStr |
Identification of a transcriptome profile associated with improvement of organ function in septic shock patients after early supportive therapy |
title_full_unstemmed |
Identification of a transcriptome profile associated with improvement of organ function in septic shock patients after early supportive therapy |
title_sort |
identification of a transcriptome profile associated with improvement of organ function in septic shock patients after early supportive therapy |
publisher |
BMC |
series |
Critical Care |
issn |
1364-8535 |
publishDate |
2018-11-01 |
description |
Abstract 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. |
topic |
Critical illness SOFA score Gene expression RNA-Seq Septic shock |
url |
http://link.springer.com/article/10.1186/s13054-018-2242-3 |
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