Decreased CX3CR1 messenger RNA expression is an independent molecular biomarker of early and late mortality in critically ill patients

Abstract

BackgroundChemokine (C-X3-C motif) receptor 1 (CX3CR1) was identified as the most differentially expressed gene between survivors and non-survivors in two independent cohorts of septic shock patients and was proposed as a marker of sepsis-induced immunosuppression. Whether such a biomarker is associated with mortality in the heterogeneous group of critically ill patients is unknown. The primary objective of this study was to evaluate the association between CX3CR1 messenger RNA (mRNA) expression and mortality in intensive care unit (ICU) patients. The secondary objective was to evaluate similar endpoints in the subgroup of septic shock patients.MethodsWe performed a prospective, multicentre, non-interventional study in six ICUs of university hospitals in Lyon, France. Every consecutive adult patient with systemic inflammatory response syndrome and an expected length of stay in the ICU over 2 days was included. Whole-blood CX3CR1 mRNA expression was measured by quantitative real-time polymerase chain reaction at day 1 (D1) and D3 after inclusion.ResultsIn ICU patients (n = 725), decreased CX3CR1 mRNA expression at D1 was associated with high D7 mortality (AUC 0.70, adjusted OR [aOR] 2.03, 95 % CI 1.19–3.46), while decreased expression at D3 was associated with increased D28 mortality (AUC 0.64, aOR 2.34, 95 % CI 1.45–3.77). In septic shock patients (n = 279), similar associations were observed between decreased D1 CX3CR1 mRNA expression and D7 mortality (AUC 0.69, aOR 2.76, 95 % CI 1.32–5.75) as well as decreased D3 expression and D28 mortality (AUC 0.72, aOR 3.98, 95 % CI 1.72–9.23). These associations were independent of lactacidaemia, Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment score and Charlson comorbidity index.ConclusionsThis study represents the largest evaluation of such an mRNA marker in a heterogeneous cohort of severely injured patients. Our results show that decreased CX3CR1 mRNA expression is associated with increased mortality in ICU patients. This suggests a link between injury-induced immunosuppression and mortality in critically ill patients. In this context, the monitoring of such a host response molecular biomarker could prove very helpful for the identification of patients at high risk of death in the ICU.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1362-x) contains supplementary material, which is available to authorized users.

Endogenous retroviruses transcriptional modulation after severe infection, trauma and burn

“…Relative standard curves describing the PCR efficiency of selected targets were created and used to perform efficiency-corrected quantification with the LightCycler Relative Quantification Software. Targets expression normalization was performed using a selected housekeeping gene (hypoxanthine phosphoribosyltransferase 1 [HPRT1, (Friggeri et al 2016)]), and results were expressed as normalized concentration ratio.…”

Dynamic LTR retrotransposon transcriptome landscape in septic shock patients

“…We found that 193 probesets, which represented 168 distinct HERV/MaLR loci, were differentially expressed in septic shock patients, depending on their immunosuppression status at day 3. The potential for stratification using these HERV/MaLR loci was validated on an independent cohort, with the identification of a severely affected group that had higher SOFA scores, decreased CX3CR1 expression (molecular marker associated with survival) [38], decreased CD74 and mHLA-DR expression (associated with HAI) [28,55], and increased S100A9 expression (associated with increased risk of secondary infections and mortality) [56]. As this pilot study was designed as a proof of concept study to show that HERV transcriptome can reflect the immune status, larger studies that involve higher numbers of patients are now warranted.…”

“…Lastly, when we examined the expression of molecular markers, all were significantly different between the two clusters. The markers were HLA-DRA [36], S100A9 [37], CX3CR1 [38] expression on day 3, and CD74 ratio (D3/D1) [28], which are all linked to the immune system and were previously shown to be prognostic biomarkers (with either mortality or secondary infections) ( Table 2 and extended Additional file 8: Table S3). Severity criteria, outcomes, and molecular markers confirmed that cluster 1 contains more severely affected patients.…”

Rapid testing of red blood cells, white blood cells and platelets in intensive care patients using the HemoScreen™ point-of-care analyzer

“…Apart from surgical control of bleeding, management of major hemorrhage may include massive transfusions to maintain adequate circulation and hemostasis [6][7][8][9][10][11]. The transfusions include packed red blood cells (RBCs), plasma, and platelets (PLTs) [12,13].…”

“…The most important parameters to monitor in intensive care units are WBC, RBC and PLTs [21]. Current European guidelines on the management of hemorrhage following trauma [6] recommend early and repeated monitoring of PLT count to predict the proper PLT transfusion regimen. In patients with ongoing bleeding frequent bedside measurement of PLT count could aid the clinician in transfusing or withholding PLTs.…”