Skip to main content
main-content

01.12.2018 | Research | Ausgabe 1/2018 Open Access

Critical Care 1/2018

Identification of a transcriptome profile associated with improvement of organ function in septic shock patients after early supportive therapy

Zeitschrift:
Critical Care > Ausgabe 1/2018
Autoren:
Matteo Barcella, Bernardo Bollen Pinto, Daniele Braga, Francesca D’Avila, Federico Tagliaferri, Marie-Angelique Cazalis, Guillaume Monneret, Antoine Herpain, Karim Bendjelid, Cristina Barlassina
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s13054-018-2242-3) contains supplementary material, which is available to authorized users.
Matteo Barcella, Bernardo Bollen Pinto, Karim Bendjelid and Cristina Barlassina contributed equally to this work.

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.
Zusatzmaterial
Additional file 6: Table S4. Gene Ontology (GO) enriched clusters obtained from differentially expressed gene (DEG) list – full table in responder (R) patients. This table is an extended and more detailed version of Table 2. All of the 66 significantly enriched GO terms are described, and we specify whether the GO term is found exclusively in Rs or in both Rs and non-responders (NRs) (Patient condition). (XLSX 17 kb)
Additional file 7: Table S5. Gene Ontology (GO) enriched clusters obtained from differentially expressed gene (DEG) list – full table in non-responder (NR) patients. This table is an extended and more detailed version of Table 3. All of the 48 significantly enriched GO terms are described, and we specify whether the GO term is found exclusively in NRs or in both responders (Rs) and NRs (Patient condition). (XLSX 16 kb)
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2018

Critical Care 1/2018 Zur Ausgabe

Neu im Fachgebiet AINS

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update AINS und bleiben Sie gut informiert – ganz bequem per eMail.

Bildnachweise