Proteomic Profiles of Exosomes of Septic Patients Presenting to the Emergency Department Compared to Healthy Controls
Background: 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. Li...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/9/9/2930 |
| _version_ | 1797554029726793728 |
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| author | Daniel C. Morris Anja K. Jaehne Michael Chopp Zhanggang Zhang Laila Poisson Yalei Chen Indrani Datta Emanuel P. Rivers |
| author_facet | Daniel C. Morris Anja K. Jaehne Michael Chopp Zhanggang Zhang Laila Poisson Yalei Chen Indrani Datta Emanuel P. Rivers |
| author_sort | Daniel C. Morris |
| collection | DOAJ |
| description | Background: 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 profiles of plasma derived exosomes obtained from septic ED patients and healthy controls. Methods: This is a prospective observational pilot study evaluating a plasma proteomic exosome profile at an urban tertiary care hospital ED using a single venipuncture blood draw, collecting 40 cc Ethylenediaminetetraacetic acid (EDTA) blood. Measurements: We recruited seven patients in the ED within 6 h of their presentation and five healthy controls. Plasma exosomes were isolated using the 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, <i>p</i>-value < 0.05. Adjustments using the 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, three 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 Δ and Fc-fragment of IgG binding protein were increased. Conclusion: Exosome proteomic profiles of septic ED patients differ from their healthy counterparts with regard to acute phase response and inflammation. |
| first_indexed | 2024-03-10T16:25:00Z |
| format | Article |
| id | doaj.art-ed41508b25234df5bfcde4552fee4f48 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T16:25:00Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-ed41508b25234df5bfcde4552fee4f482023-11-20T13:20:30ZengMDPI AGJournal of Clinical Medicine2077-03832020-09-0199293010.3390/jcm9092930Proteomic Profiles of Exosomes of Septic Patients Presenting to the Emergency Department Compared to Healthy ControlsDaniel C. Morris0Anja K. Jaehne1Michael Chopp2Zhanggang Zhang3Laila Poisson4Yalei Chen5Indrani Datta6Emanuel P. Rivers7Department of Emergency Medicine, Henry Ford Hospital, Detroit, MI 48202, USADepartment of Emergency Medicine, Henry Ford Hospital, Detroit, MI 48202, USADepartment of Neurology Research, Henry Ford Hospital, Detroit, MI 48202, USADepartment of Neurology Research, Henry Ford Hospital, Detroit, MI 48202, USADepartment of Public Health Sciences, Henry Ford Hospital, Detroit, MI 48202, USADepartment of Public Health Sciences, Henry Ford Hospital, Detroit, MI 48202, USADepartment of Public Health Sciences, Henry Ford Hospital, Detroit, MI 48202, USADepartment of Emergency Medicine, Henry Ford Hospital, Detroit, MI 48202, USABackground: 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 profiles of plasma derived exosomes obtained from septic ED patients and healthy controls. Methods: This is a prospective observational pilot study evaluating a plasma proteomic exosome profile at an urban tertiary care hospital ED using a single venipuncture blood draw, collecting 40 cc Ethylenediaminetetraacetic acid (EDTA) blood. Measurements: We recruited seven patients in the ED within 6 h of their presentation and five healthy controls. Plasma exosomes were isolated using the 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, <i>p</i>-value < 0.05. Adjustments using the 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, three 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 Δ and Fc-fragment of IgG binding protein were increased. Conclusion: Exosome proteomic profiles of septic ED patients differ from their healthy counterparts with regard to acute phase response and inflammation.https://www.mdpi.com/2077-0383/9/9/2930sepsisseptic shockexosomesproteomic profileshealthy volunteersemergency department |
| spellingShingle | Daniel C. Morris Anja K. Jaehne Michael Chopp Zhanggang Zhang Laila Poisson Yalei Chen Indrani Datta Emanuel P. Rivers Proteomic Profiles of Exosomes of Septic Patients Presenting to the Emergency Department Compared to Healthy Controls Journal of Clinical Medicine sepsis septic shock exosomes proteomic profiles healthy volunteers emergency department |
| title | Proteomic Profiles of Exosomes of Septic Patients Presenting to the Emergency Department Compared to Healthy Controls |
| title_full | Proteomic Profiles of Exosomes of Septic Patients Presenting to the Emergency Department Compared to Healthy Controls |
| title_fullStr | Proteomic Profiles of Exosomes of Septic Patients Presenting to the Emergency Department Compared to Healthy Controls |
| title_full_unstemmed | Proteomic Profiles of Exosomes of Septic Patients Presenting to the Emergency Department Compared to Healthy Controls |
| title_short | Proteomic Profiles of Exosomes of Septic Patients Presenting to the Emergency Department Compared to Healthy Controls |
| title_sort | proteomic profiles of exosomes of septic patients presenting to the emergency department compared to healthy controls |
| topic | sepsis septic shock exosomes proteomic profiles healthy volunteers emergency department |
| url | https://www.mdpi.com/2077-0383/9/9/2930 |
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