Decrease of exosomal miR-21-5p and the increase of CD62p+ exosomes are associated with the development of sepsis in polytraumatized patients
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Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury
Published on: May 21, 2018
Birte Weber1, Dirk Henrich1, Ingo Marzi1
1Goethe-University, University Hospital Frankfurt, Department of Trauma-, Hand- and Reconstructive Surgery, Frankfurt am Main, Germany.
Insights
Early detection of sepsis in polytrauma patients is crucial. Exosomes show promise, with increased CD62p+ exosomes and decreased miR-21-5p indicating sepsis development.
Area of Science:
- Biomedical research
- Trauma and critical care medicine
- Molecular diagnostics
Background:
- Sepsis is a leading cause of death in polytrauma patients, necessitating early detection for improved outcomes.
- Exosomes, small extracellular vesicles, are emerging as potential biomarkers for diagnosing complications in critically ill patients.
- Current diagnostic methods may not provide timely detection of sepsis onset in the complex polytrauma setting.
Purpose of the Study:
- To investigate the potential of exosomes and their cargo as early diagnostic markers for sepsis in polytrauma patients.
- To compare exosomal surface marker expression and miRNA profiles between septic and non-septic polytrauma patients and healthy controls.
- To correlate exosomal cytokine levels with systemic cytokine concentrations.
Main Methods:
- Plasma samples were collected from polytraumatized patients (Injury Severity Score ≥16) with and without sepsis, and from healthy controls.
- Extracellular vesicle (EV) subpopulations were analyzed using multiplex flow cytometry for surface epitopes.
- Exosomal cytokine concentrations were measured by high-sensitive ELISA, and miRNA cargo was analyzed via RT-qPCR.
Main Results:
- Septic polytrauma patients showed a significant increase in CD62p+ exosomes compared to non-septic patients and controls.
- CD40+ and CD49e+ exosome levels were significantly diminished in septic polytrauma patients.
- A decrease in exosomal miR-21-5p was associated with sepsis development, while exosomal IL-6 reflected systemic levels.
Conclusions:
- Increased CD62p+ exosomes serve as a potential indicator for sepsis development in polytrauma patients.
- Alterations in exosomal miRNA cargo, specifically decreased miR-21-5p, are associated with sepsis in this patient cohort.
- Exosomes represent a promising avenue for early sepsis detection and monitoring in polytrauma, aiding clinical decision-making.
Abstract:
Sepsis as a severe systemic inflammation leads oftentimes to organ dysfunction and subsequently to death. In polytrauma patients, septic complications represent with 45% the predominant cause of late death and are responsible for extremely high costs in the healthcare system. Therefore, clinicians have to detect as early as possible the begin of sepsis to improve the patient's outcome. One new promising diagnostic tool to diagnose septic complications in polytraumatized patients are exosomes. Plasma samples from polytraumatized patients (Injury Severity Score (ISS) ≥16) which developed sepsis (n = 10) and without sepsis (n = 10), were collected at emergency room (ER), 24h and 5 days after trauma. The EVs subpopulations were investigated by a bead-based multiplex flow cytometry measurement of surface epitopes and were compared with plasma EVs from healthy controls (n = 10). Moreover, exosomal cytokine concentrations were measured via high-sensitive ELISA and were correlated with systemic concentrations. For miRNA cargo analysis, we analysed the miRNAs miR-1298-5p, miR-1262, miR-125b-5p, miR-92a-3p, miR-93-5p, miR-155-5p and miR-21-5p and compared their exosomal concentrations by means of RT-qPCR. CD62p + exosomes were significantly increased in septic polytrauma-patients (p ≤ 0.05), while CD40+exosomes, as well as CD49e + exosomes were diminished (p ≤ 0.05). Furthermore, we observed that the exosomal IL-6 concentration reflects the systemic IL-6 concentration (r2 = 0.63) and did not significantly alter between patients with and without sepsis. The exosomal IL-10 concentration seemed to be constant in all patients and healthy controls. We observed that a decrease of miR-21-5p in exosomes was associated with the development of sepsis (p ≤ 0.05), while exosomal miR-93-5p, miR-155-5p and miR-92a-3p were not specifically altered in septic patients. Taken together, the present study in polytraumatized patients demonstrated that the development of sepsis is associated with an increase of CD62p + exosomes. Furthermore, the exosomal cargo was changed in septic patients: miR-21-5p was diminished.
