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Multicenter Study
. 2017 Jul;43(7):1013-1020.
doi: 10.1007/s00134-017-4805-1. Epub 2017 May 5.

Association between mRNA expression of CD74 and IL10 and risk of ICU-acquired infections: a multicenter cohort study

Estelle Peronnet  1   2 , Fabienne Venet  3   4   5 , Delphine Maucort-Boulch  6   7   8   9 , Arnaud Friggeri  4   10   11 , Martin Cour  12 , Laurent Argaud  12 , Bernard Allaouchiche  10 , Bernard Floccard  13 , Frédéric Aubrun  14 , Thomas Rimmelé  3   4   13 , Fabrice Thiolliere  10 , Vincent Piriou  10 , Julien Bohé  10 , Marie-Angélique Cazalis  3   4 , Véronique Barbalat  3   4 , Guillaume Monneret  3   4   5 , Stéphane Morisset  3   4 , Julien Textoris  3   4   13 , Hélène Vallin  3   4   10 , Alexandre Pachot  3   4 , Alain Lepape  4   10   11 ; MIP Rea Study Group
Affiliations
Multicenter Study

Association between mRNA expression of CD74 and IL10 and risk of ICU-acquired infections: a multicenter cohort study

Estelle Peronnet et al. Intensive Care Med. 2017 Jul.

Abstract

Purpose: Intensive care unit (ICU)-acquired infections (IAI) result in increased hospital and ICU stay, costs and mortality. To date, no biomarker has shown sufficient evidence and ease of application in clinical routine for the identification of patients at risk of IAI. We evaluated the association of the systemic mRNA expression of two host response biomarkers, CD74 and IL10, with IAI occurrence in a large cohort of ICU patients.

Methods: ICU patients were prospectively enrolled in a multicenter cohort study. Whole blood was collected on the day of admission (D1) and on day 3 (D3) and day 6 (D6) after admission. Patients were screened daily for IAI occurrence and data were censored after IAI diagnosis. mRNA expression levels of biomarkers were measured using RT-qPCR. Fine and Gray competing risk models were used to assess the association between gene expression and IAI occurrence.

Results: A total of 725 patients were analyzed. At least one IAI episode occurred in 137 patients (19%). After adjustment for shock and sepsis status at admission, CD74 and IL10 levels were found to be significantly associated with IAI occurrence [subdistribution hazard ratio (95% confidence interval) 0.67 (0.46-0.97) for CD74 D3/D1 expression ratio and 2.21 (1.63-3.00) for IL10 at D3]. IAI cumulative incidence was significantly different between groups stratified according to CD74 or IL10 expression (Gray tests p < 0.001).

Conclusion: Our results suggest that two immune biomarkers, CD74 and IL10, could be relevant tools for the identification of IAI risk in ICU patients.

Keywords: Biomarkers; CD74; Cross-infections; IL10; Immune monitoring; Intensive care unit.

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Conflict of interest statement

Conflicts of interest

All authors are employees of either bioMerieux (EP, MAC, VB, JT and AP) or the University Hospital of Lyon (FV, DMB, AF, MC, LA, BA, BF, FA, TR, FT, VP, JB, GM, SM, HV and AL). This project is part of Advanced Diagnostics for New Therapeutic Approaches, a program dedicated to personalized medicine, coordinated by Institut Mérieux, and supported by the French public agency BPI (Banque Publique d’Investissement). TR reports non-financial support from Fresenius Medical Care, as well as grants, personal fees and non-financial support from Gambro Baxter, unconnected with the submitted work.

Fundings

This study was funded by University Hospital of Lyon, bioMérieux and Advanced Diagnostics for New Therapeutic Approaches, a program dedicated to personalized medicine, coordinated by Institut Mérieux and supported by the French public agency BPI (Banque Publique d’Investissement). bioMérieux and Lyon University Hospital were co-responsible for the study design, collection of data, interpretation of results, and writing of the report. BPI had no active role in the study.

Figures

Fig. 1
Fig. 1
Adjusted Fine and Gray subdistribution hazard ratios and 95 confidence intervals for IAI occurrence in multivariate analysis. For each individual time-points, models were computed adjusting for shock and sepsis status at admission as covariates (see Supplementary Table 3 for details). For IL10 mRNA levels, subdistribution hazard ratios are expressed for an increase of 0.1 unit. ICU intensive care unit, IAI ICU-acquired infection
Fig. 2
Fig. 2
Cumulative incidence of first IAI episode in percentage, in populations defined by the CD74 D3/D1 ratio (a) or IL10 at D3 (b). For each biomarker, the threshold was selected to maximize the Youden index (1.238 for CD74 D3/D1 expression ratio and 0.039 for IL10 at D3). For each group, curves were represented until the end of patient follow-up, defined by the occurrence of the first event among IAI, discharge alive without IAI or death without IAI. A significant difference was obtained between the two curves for the CD74 D3/D1 ratio (Gray test p < 0.001) and for IL10 at D3 (Gray test p < 0.001). ICU intensive care unit, IAI ICU-acquired infection
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Comment in

References

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