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

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

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.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Antigens, Differentiation, B-Lymphocyte / blood*
  • Antigens, Differentiation, B-Lymphocyte / genetics
  • Biomarkers / blood
  • Cross Infection / diagnosis
  • Cross Infection / epidemiology*
  • Female
  • Gene Expression Regulation
  • Histocompatibility Antigens Class II / blood*
  • Histocompatibility Antigens Class II / genetics
  • Hospitalization
  • Humans
  • Incidence
  • Intensive Care Units* / statistics & numerical data
  • Interleukin-10 / blood*
  • Interleukin-10 / genetics
  • Male
  • Prospective Studies
  • RNA, Messenger / blood
  • RNA, Messenger / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Assessment

Substances

  • Antigens, Differentiation, B-Lymphocyte
  • Biomarkers
  • Histocompatibility Antigens Class II
  • RNA, Messenger
  • invariant chain
  • Interleukin-10