MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis
Abstract Background Currently, no suitable clinical marker for detection of septic immunosuppression is available. We aimed at identifying microRNAs that could serve as biomarkers of T-cell mediated immunoparalysis in sepsis. Methods RNA was isolated from purified T-cells or from whole blood cells o...
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doaj-b70e8d84959543bba1665ae18c48e65c2020-11-25T01:19:57ZengBMCMolecular Medicine1076-15511528-36582018-10-0124111410.1186/s10020-018-0056-zMicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsisP Möhnle0S Hirschberger1L C Hinske2J Briegel3M Hübner4S Weis5G Dimopoulos6M Bauer7E J Giamarellos-Bourboulis8S Kreth9Department of Anaesthesiology and Intensive Care Medicine, University Hospital, Ludwig Maximilian University (LMU)Department of Anaesthesiology and Intensive Care Medicine, University Hospital, Ludwig Maximilian University (LMU)Department of Anaesthesiology and Intensive Care Medicine, University Hospital, Ludwig Maximilian University (LMU)Department of Anaesthesiology and Intensive Care Medicine, University Hospital, Ludwig Maximilian University (LMU)Department of Anaesthesiology and Intensive Care Medicine, University Hospital, Ludwig Maximilian University (LMU)Department of Anaesthesiology and Intensive Care Medicine, Friedrich-Schiller University2nd Department of Critical Care Medicine, ATTIKON University Hospital, National and Kapodistrian University of AthensDepartment of Anaesthesiology and Intensive Care Medicine, Friedrich-Schiller University4th Department of Internal Medicine, ATTIKON University Hospital, National and Kapodistrian University of AthensDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital, Ludwig Maximilian University (LMU)Abstract Background Currently, no suitable clinical marker for detection of septic immunosuppression is available. We aimed at identifying microRNAs that could serve as biomarkers of T-cell mediated immunoparalysis in sepsis. Methods RNA was isolated from purified T-cells or from whole blood cells obtained from septic patients and healthy volunteers. Differentially regulated miRNAs were identified by miRNA Microarray (n = 7). Validation was performed via qPCR (n = 31). Results T-cells of septic patients revealed characteristics of immunosuppression: Pro-inflammatory miR-150 and miR-342 were downregulated, whereas anti-inflammatory miR-15a, miR-16, miR-93, miR-143, miR-223 and miR-424 were upregulated. Assessment of T-cell effector status showed significantly reduced mRNA-levels of IL2, IL7R and ICOS, and increased levels of IL4, IL10 and TGF-β. The individual extent of immunosuppression differed markedly. MicroRNA-143, − 150 and − 223 independently indicated T-cell immunoparalysis and significantly correlated with patient’s IL7R-/ICOS-expression and SOFA-scores. In whole blood, composed of innate and adaptive immune cells, both traits of immunosuppression and hyperinflammation were detected. Importantly, miR-143 and miR-150 – both predominantly expressed in T-cells – retained strong power of discrimination also in whole blood samples. Conclusions These findings suggest miR-143 and miR-150 as promising markers for detection of T-cell immunosuppression in whole blood and may help to develop new approaches for miRNA-based diagnostic in sepsis.http://link.springer.com/article/10.1186/s10020-018-0056-zSepsisImmunoparalysisT-cellsT cell exhaustionmiRNABiomarker |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
P Möhnle S Hirschberger L C Hinske J Briegel M Hübner S Weis G Dimopoulos M Bauer E J Giamarellos-Bourboulis S Kreth |
spellingShingle |
P Möhnle S Hirschberger L C Hinske J Briegel M Hübner S Weis G Dimopoulos M Bauer E J Giamarellos-Bourboulis S Kreth MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis Molecular Medicine Sepsis Immunoparalysis T-cells T cell exhaustion miRNA Biomarker |
author_facet |
P Möhnle S Hirschberger L C Hinske J Briegel M Hübner S Weis G Dimopoulos M Bauer E J Giamarellos-Bourboulis S Kreth |
author_sort |
P Möhnle |
title |
MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis |
title_short |
MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis |
title_full |
MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis |
title_fullStr |
MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis |
title_full_unstemmed |
MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis |
title_sort |
micrornas 143 and 150 in whole blood enable detection of t-cell immunoparalysis in sepsis |
publisher |
BMC |
series |
Molecular Medicine |
issn |
1076-1551 1528-3658 |
publishDate |
2018-10-01 |
description |
Abstract Background Currently, no suitable clinical marker for detection of septic immunosuppression is available. We aimed at identifying microRNAs that could serve as biomarkers of T-cell mediated immunoparalysis in sepsis. Methods RNA was isolated from purified T-cells or from whole blood cells obtained from septic patients and healthy volunteers. Differentially regulated miRNAs were identified by miRNA Microarray (n = 7). Validation was performed via qPCR (n = 31). Results T-cells of septic patients revealed characteristics of immunosuppression: Pro-inflammatory miR-150 and miR-342 were downregulated, whereas anti-inflammatory miR-15a, miR-16, miR-93, miR-143, miR-223 and miR-424 were upregulated. Assessment of T-cell effector status showed significantly reduced mRNA-levels of IL2, IL7R and ICOS, and increased levels of IL4, IL10 and TGF-β. The individual extent of immunosuppression differed markedly. MicroRNA-143, − 150 and − 223 independently indicated T-cell immunoparalysis and significantly correlated with patient’s IL7R-/ICOS-expression and SOFA-scores. In whole blood, composed of innate and adaptive immune cells, both traits of immunosuppression and hyperinflammation were detected. Importantly, miR-143 and miR-150 – both predominantly expressed in T-cells – retained strong power of discrimination also in whole blood samples. Conclusions These findings suggest miR-143 and miR-150 as promising markers for detection of T-cell immunosuppression in whole blood and may help to develop new approaches for miRNA-based diagnostic in sepsis. |
topic |
Sepsis Immunoparalysis T-cells T cell exhaustion miRNA Biomarker |
url |
http://link.springer.com/article/10.1186/s10020-018-0056-z |
work_keys_str_mv |
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