title: Cellular and extracellular miRNAs are blood-compartment-specific diagnostic targets in sepsis.
abstract: Septic shock is a common medical condition with a mortality approaching 50% where early diagnosis and treatment are of particular importance for patient survival. Novel biomarkers that serve as prompt indicators of sepsis are urgently needed. High-throughput technologies assessing circulating microRNAs represent an important tool for biomarker identification, but the blood-compartment specificity of these miRNAs has not yet been investigated. We characterized miRNA profiles from serum exosomes, total serum and blood cells (leukocytes, erythrocytes, platelets) of sepsis patients by next-generation sequencing and RT-qPCR (n = 3 × 22) and established differences in miRNA expression between blood compartments. In silico analysis was used to identify compartment-specific signalling functions of differentially regulated miRNAs in sepsis-relevant pathways. In septic shock, a total of 77 and 103 miRNAs were down- and up-regulated, respectively. A majority of these regulated miRNAs (14 in serum, 32 in exosomes and 73 in blood cells) had not been previously associated with sepsis. We found a distinctly compartment-specific regulation of miRNAs between sepsis patients and healthy volunteers. Blood cellular miR-199b-5p was identified as a potential early indicator for sepsis and septic shock. miR-125b-5p and miR-26b-5p were uniquely regulated in exosomes and serum, respectively, while one miRNA (miR-27b-3p) was present in all three compartments. The expression of sepsis-associated miRNAs is compartment-specific. Exosome-derived miRNAs contribute significant information regarding sepsis diagnosis and survival prediction and could serve as newly identified targets for the development of novel sepsis biomarkers.
authors.affiliation: Institute of Human Genetics, University Hospital, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Marlene
authors.identifier: 0000-0002-9113-9643
authors.initials: M
authors.lastname: Reithmair
authors.affiliation: Institute of Human Genetics, University Hospital, Ludwig-Maximilians-University, Munich, Germany.|Division of Animal Physiology and Immunology, TUM School of Life Sciences Weihenstephan, Technical University Munich, Munich, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Buschmann
authors.affiliation: Department of Anesthesiology, University Hospital, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Märte
authors.affiliation: Division of Animal Physiology and Immunology, TUM School of Life Sciences Weihenstephan, Technical University Munich, Munich, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Kirchner
authors.affiliation: Department of Anesthesiology, University Hospital, Ludwig-Maximilians-University, Munich, Germany.|Department of Anaesthesiology, Neuperlach Hospital, City Hospitals of Munich, Munich, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hagl
authors.affiliation: Department of Anaesthesiology, Neuperlach Hospital, City Hospitals of Munich, Munich, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Kaufmann
authors.affiliation: Institute of Human Genetics, University Hospital, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Pfob
authors.affiliation: Department of Anesthesiology, University Hospital, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Chouker
authors.affiliation: Institute of Human Genetics, University Hospital, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Ortrud K
authors.initials: OK
authors.lastname: Steinlein
authors.affiliation: Division of Animal Physiology and Immunology, TUM School of Life Sciences Weihenstephan, Technical University Munich, Munich, Germany.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Pfaffl
authors.affiliation: Department of Anesthesiology, University Hospital, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Gustav
authors.initials: G
authors.lastname: Schelling
mesh_terms: D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D055354:Exosomes / Q000235:genetics* / Q000648:ultrastructure; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D046529:Microscopy, Electron, Transmission; D011379:Prognosis; D018805:Sepsis / Q000097:blood / Q000175:diagnosis / Q000235:genetics*
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: biomarker; blood compartment; exosome; liquid biopsy; miRNA; sepsis