Proteomics

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Proteomic Profiles of Exosomes of Septic Patients Presenting to the Emergency Department Compared to Healthy Controls


ABSTRACT: Background: Septic Emergency Department (ED) patients provide a unique opportunity to investigate early sepsis. Recent work focuses on exosomes, nanoparticle-sized lipid vesicles (30-130nm) that are released into the bloodstream to transfer its contents (RNA, miRNA, DNA, protein) to other cells. Little is known how exosomes may contribute to the dysregulated inflammatory septic response that leads to multi-organ dysfunction. We aimed to evaluate proteomic profiles of plasma derived exosomes obtained from septic ED patients and healthy controls. Methods: This is a prospective observational pilot study evaluating plasma exosome profile at an urban tertiary care hospital ED using a single venipuncture blood draw, collecting 40 cc EDTA blood. Measurements: We recruited 7 patients and 5 healthy controls. Plasma exosomes were isolated using Invitrogen Total Exosome Isolation Kit. Exosome proteomic profiles were analyzed using fusion mass spectroscopy and Proteome Discoverer. Principal component analysis (PCA) and differential expression analysis (DEA) for sepsis versus control was performed. Results: PCA of 261 proteins demonstrated septic patients and healthy controls were distributed in two groups. DEA revealed that 62 (23.8%) proteins differed between the exosomes of septic patients and healthy controls, p-value <0.05. Adjustments using False Discovery Rate (FDR) showed 23 proteins remained significantly different (FDR<0.05) between sepsis and controls. Septic patients and controls were classified into two distinct groups by hierarchical clustering using the 62 nominally DE proteins. After adjustment multiple comparisons, 3 acute phase proteins remained significantly different between patients and controls: Serum amyloid A-1, C-reactive protein and Serum Amyloid A-2. Inflammatory response proteins immunoglobulin heavy constant delta and Fc-fragment of IgG binding protein were increased. Conclusion: Exosome proteomic profiles of septic ED patients differ from their healthy counterparts in regard to acute phase response and inflammation.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Emanuel P Rivers  

PROVIDER: MSV000085646 | MassIVE | Mon Jun 29 09:14:00 BST 2020

SECONDARY ACCESSION(S): PXD020106

REPOSITORIES: MassIVE

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Proteomic Profiles of Exosomes of Septic Patients Presenting to the Emergency Department Compared to Healthy Controls.

Morris Daniel C DC   Jaehne Anja K AK   Chopp Michael M   Zhang Zhanggang Z   Poisson Laila L   Chen Yalei Y   Datta Indrani I   Rivers Emanuel P EP  

Journal of clinical medicine 20200911 9


<h4>Background</h4>Septic Emergency Department (ED) patients provide a unique opportunity to investigate early sepsis. Recent work focuses on exosomes, nanoparticle-sized lipid vesicles (30-130 nm) that are released into the bloodstream to transfer its contents (RNA, miRNA, DNA, protein) to other cells. Little is known about how early changes related to exosomes may contribute to the dysregulated inflammatory septic response that leads to multi-organ dysfunction. We aimed to evaluate proteomic p  ...[more]

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