LiBOD – Liquid Biopsy in Organ Damage – small extracellular vesicle chip-based assessment of polytrauma
WANG B. 1, WÖHLER A. 2, SALZMANN R. 1,4, KELLER C. 1,4, TERTEL T. 3, SCHAAF S. 2, SCHWAB R. 2, GIEBEL B. 3, LUKACS-KORNEK V. 4, WILLMS A. 4,5, KORNEK M. 1
1 University Hospital Bonn of the Rheinische Friedrich-Wilhelms-University, Bonn, Germany; 2 Department of General, Visceral and Thoracic Surgery, German Armed Forces Central Hospital, Koblenz, Germany; 3 Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany; 4 Institute of Molecular Medicine and Experimental Immunology, University Hospital Bonn of the Rheinische Friedrich-Wilhelms-University, Bonn, Germany; 5 Department of General and Visceral Surgery, German Armed Forces Hospital, Hamburg, Germany
Objective: Our Liquid Biopsy in Organ Damage (LiBOD) study aimed to differentiate polytrauma patients (Injury Severity Score (ISS) ≥ 15) with internal organ injury from polytrauma patients without organ injury. Small extracellular vesicles (sEVs) were isolated from human blood collected after trauma and quantified. Results were validated in a porcine polytrauma model.
Background Data: Despite major advances in medicine, blood-borne biomarkers are urgently needed to support decision-making, including polytrauma. Here, we assessed serum-derived extracellular vesicles as potential decision-makers in polytrauma.
Methods: sEVs from 61 polytrauma (ISS ≥ 15) patients’ sera were isolated by size exclusion chromatography. Particle counts were measured by nanoparticle tracking analysis. sEVs were captured on a microarray chip coated with anti-CD9, anti-CD63 and anti-CD81 and surface stained with fluorescently labelled anti-CD14 and anti-CD61 antibodies. Surface analysis of sEVs on a single particle level was performed with ExoView® R100 (NanoView Biosciences, Boston, USA). Data analysis was performed using ExoView® Analyzer 3.2.
Results: We found that blood-borne sEVs derived from monocytes (CD14+ sEVs), platelets, and their precursors (CD61+ sEVs) were significantly increased in patients with polytrauma and organ damage. Actually, CD9+CD14+ sEVs were superior and reached a sensitivity and specificity of 0.81% and 0.97%, respectively. Additionally, we observed a marked and significant decrease in CD9+CD14+ and CD9+CD61+ sEVs 7 days after trauma compared with 24-hour values in patients who did not develop any post-trauma complications such as systemic inflammatory response syndrome, acute respiratory distress syndrome, or sepsis.
Conclusions: Blood-borne sEVs from monocytes, platelets, and their precursors may be potential candidates as novel objective biomarkers in polytrauma. Overall, an sEVs assessment as part of LiBOD has the potential to assist subjective triage with an objected value to prevent under and over triage and to assist in providing the best and fastest medical care for trauma patients.