Exosomal CD63 in critically ill patients with sepsis

Abstract CD63 is one of the tetraspanin protein family members that is ubiquitously expressed on exosomes and is involved in the signal transduction of various types of immune cells. It may thus contribute to immunometabolic mechanisms of cellular and organ dysfunction in sepsis. Nonetheless, the as...

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Main Authors: Yunjoo Im, Hongseok Yoo, Ryoung-Eun Ko, Jin Young Lee, Junseon Park, Kyeongman Jeon
Format: Article
Language:English
Published: Nature Portfolio 2021-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-99777-w
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author Yunjoo Im
Hongseok Yoo
Ryoung-Eun Ko
Jin Young Lee
Junseon Park
Kyeongman Jeon
author_facet Yunjoo Im
Hongseok Yoo
Ryoung-Eun Ko
Jin Young Lee
Junseon Park
Kyeongman Jeon
author_sort Yunjoo Im
collection DOAJ
description Abstract CD63 is one of the tetraspanin protein family members that is ubiquitously expressed on exosomes and is involved in the signal transduction of various types of immune cells. It may thus contribute to immunometabolic mechanisms of cellular and organ dysfunction in sepsis. Nonetheless, the association of exosomal CD63 with the severity and mortality of sepsis is not well known. Therefore, in the present study, the overall levels of exosomal CD63 were evaluated to ascertain whether they were associated with organ failure and mortality in patients with sepsis. Exosomal CD63 was measured from prospectively enrolled critically-ill patients with sepsis (n = 217) and healthy control (n = 20). To detect and quantify exosomes in plasma, a commercially available enzyme-linked immunosorbent assay kit was used according to the manufacturer’s protocol. The total number of exosomal CD63 was determined by quantifying the immunoreactive CD63. The association between plasma levels of exosomal CD63 and sequential organ failure assessment (SOFA) score was assessed by a linear regression method. The best cut-off level of exosomal CD63 for 28-day mortality prediction was determined by Youden’s index. Among 217 patients with sepsis, 143 (66%) patients were diagnosed with septic shock. Trends of increased exosomal CD63 levels were observed in control, sepsis, and septic-shock groups (6.6 µg/mL vs. 42 µg/mL vs. 90 µg/mL, p < 0.001). A positive correlation between exosomal CD63 and SOFA scores was observed in patients with sepsis (r value = 0.35). When patients were divided into two groups according to the best cut-off level, the group with higher exosomal CD63 levels (more than 126 µg/mL) was significantly associated with 28-day and in-hospital mortality. Moreover, the Kaplan–Meier survival method showed a significant difference in 90-day survival between patients with high- and low-exosomal CD63 levels (log-rank p = 0.005). Elevated levels of exosomal CD63 were associated with the severity of organ failure and predictive of mortality in critically ill patients with sepsis.
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spelling doaj.art-cece117e88df458cba6d422955dacff82022-12-21T20:09:33ZengNature PortfolioScientific Reports2045-23222021-10-011111710.1038/s41598-021-99777-wExosomal CD63 in critically ill patients with sepsisYunjoo Im0Hongseok Yoo1Ryoung-Eun Ko2Jin Young Lee3Junseon Park4Kyeongman Jeon5Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of MedicineDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of MedicineDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of MedicineAbstract CD63 is one of the tetraspanin protein family members that is ubiquitously expressed on exosomes and is involved in the signal transduction of various types of immune cells. It may thus contribute to immunometabolic mechanisms of cellular and organ dysfunction in sepsis. Nonetheless, the association of exosomal CD63 with the severity and mortality of sepsis is not well known. Therefore, in the present study, the overall levels of exosomal CD63 were evaluated to ascertain whether they were associated with organ failure and mortality in patients with sepsis. Exosomal CD63 was measured from prospectively enrolled critically-ill patients with sepsis (n = 217) and healthy control (n = 20). To detect and quantify exosomes in plasma, a commercially available enzyme-linked immunosorbent assay kit was used according to the manufacturer’s protocol. The total number of exosomal CD63 was determined by quantifying the immunoreactive CD63. The association between plasma levels of exosomal CD63 and sequential organ failure assessment (SOFA) score was assessed by a linear regression method. The best cut-off level of exosomal CD63 for 28-day mortality prediction was determined by Youden’s index. Among 217 patients with sepsis, 143 (66%) patients were diagnosed with septic shock. Trends of increased exosomal CD63 levels were observed in control, sepsis, and septic-shock groups (6.6 µg/mL vs. 42 µg/mL vs. 90 µg/mL, p < 0.001). A positive correlation between exosomal CD63 and SOFA scores was observed in patients with sepsis (r value = 0.35). When patients were divided into two groups according to the best cut-off level, the group with higher exosomal CD63 levels (more than 126 µg/mL) was significantly associated with 28-day and in-hospital mortality. Moreover, the Kaplan–Meier survival method showed a significant difference in 90-day survival between patients with high- and low-exosomal CD63 levels (log-rank p = 0.005). Elevated levels of exosomal CD63 were associated with the severity of organ failure and predictive of mortality in critically ill patients with sepsis.https://doi.org/10.1038/s41598-021-99777-w
spellingShingle Yunjoo Im
Hongseok Yoo
Ryoung-Eun Ko
Jin Young Lee
Junseon Park
Kyeongman Jeon
Exosomal CD63 in critically ill patients with sepsis
Scientific Reports
title Exosomal CD63 in critically ill patients with sepsis
title_full Exosomal CD63 in critically ill patients with sepsis
title_fullStr Exosomal CD63 in critically ill patients with sepsis
title_full_unstemmed Exosomal CD63 in critically ill patients with sepsis
title_short Exosomal CD63 in critically ill patients with sepsis
title_sort exosomal cd63 in critically ill patients with sepsis
url https://doi.org/10.1038/s41598-021-99777-w
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