Differential Gene Expression in Circulating CD14+ Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis

Journal of Clinical Medicine, vol. 9, pp. 127

Abstract

Critical illness and sepsis are characterized by drastic changes in the systemic innate immune response, particularly involving monocytes. The exact monocyte activation profile during sepsis, however, has remained obscure. Therefore, we prospectively analyzed the gene expression profile of circulating CD14+ monocytes from healthy volunteers (n = 54) and intensive care unit (ICU) patients (n = 76), of which n = 36 had sepsis. RNA sequencing of selected samples revealed that monocytes from septic ICU patients display a peculiar activation pattern, which resembles characteristic functional stages of monocyte-derived macrophages and is distinct from controls or non-sepsis ICU patients. Focusing on 55 highly variable genes selected for further investigation, arachidonate 5-lipoxygenase-activating protein (ALOX5AP) was highly upregulated in monocytes of ICU patients and only normalized during 7 days in the ICU in non-sepsis patients. Strikingly, low monocytic guanine nucleotide exchange factor 10-like protein (ARHGEF10L) mRNA expression was associated with the disease severity and mortality of ICU patients. Collectively, our comprehensive analysis of circulating monocytes in critically ill patients revealed a distinct activation pattern, particularly in ICU patients with sepsis. The association with disease severity, the longitudinal recovery or lack thereof during the ICU stay, and the association with prognosis indicate the clinical relevance of monocytic gene expression profiles during sepsis.

Authors 13

1. Anke Liepelt Aachen Department of Medicine III

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Medicine III, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany

2. Philipp Hohlstein Aachen Department of Medicine III

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Medicine III, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany

3. Hendrik Gussen Aachen Department of Anaesthesiology Department of Medicine III

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Anaesthesiology, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany

   Department of Medicine III, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany

4. Anna C. Aschenbrenner

   University of Bonn · Radboud University Nijmegen · Radboud University Medical Center

   Affiliation as printed

   Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, 6525 Nijmegen, The Netherlands

   Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany

5. Thomas Ulas

   University of Bonn

   Affiliation as printed

   Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany

6. Lukas Buendgens Aachen Department of Medicine III

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Medicine III, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany

7. Klaudia Theresa Warzecha Aachen Department of Medicine III

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Medicine III, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany

8. Matthias Bartneck Aachen Department of Medicine III

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Medicine III, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany

9. Tom Luedde Aachen Department of Medicine III

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Medicine III, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany

10. Christian Trautwein Aachen Department of Medicine III

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Department of Medicine III, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany

11. Joachim Ludwig Schultze

    University of Bonn

    Affiliation as printed

    Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany

12. Alexander Hemdorff Koch Aachen Department of Medicine III

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Department of Medicine III, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany

13. Frank Tacke corresponding Aachen Department of Medicine III

    Universitätsklinikum Aachen · Charité - Universitätsmedizin Berlin · RWTH Aachen University

    Affiliation as printed

    Department of Hepatology & Gastroenterology, Campus Virchow Klinikum and Charité Campus Mitte, Charité University Medicine Berlin, 13353 Berlin, Germany

    Department of Medicine III, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany