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MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis

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...

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Autores principales: Möhnle, P, Hirschberger, S, Hinske, L C, Briegel, J, Hübner, M, Weis, S, Dimopoulos, G, Bauer, M, Giamarellos-Bourboulis, E J, Kreth, S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191918/
https://www.ncbi.nlm.nih.gov/pubmed/30332984
http://dx.doi.org/10.1186/s10020-018-0056-z
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author Möhnle, P
Hirschberger, S
Hinske, L C
Briegel, J
Hübner, M
Weis, S
Dimopoulos, G
Bauer, M
Giamarellos-Bourboulis, E J
Kreth, S
author_facet Möhnle, P
Hirschberger, S
Hinske, L C
Briegel, J
Hübner, M
Weis, S
Dimopoulos, G
Bauer, M
Giamarellos-Bourboulis, E J
Kreth, S
author_sort Möhnle, P
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s10020-018-0056-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-61919182018-10-31 MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis Möhnle, P Hirschberger, S Hinske, L C Briegel, J Hübner, M Weis, S Dimopoulos, G Bauer, M Giamarellos-Bourboulis, E J Kreth, S Mol Med Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s10020-018-0056-z) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-17 /pmc/articles/PMC6191918/ /pubmed/30332984 http://dx.doi.org/10.1186/s10020-018-0056-z Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Möhnle, P
Hirschberger, S
Hinske, L C
Briegel, J
Hübner, M
Weis, S
Dimopoulos, G
Bauer, M
Giamarellos-Bourboulis, E J
Kreth, S
MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191918/
https://www.ncbi.nlm.nih.gov/pubmed/30332984
http://dx.doi.org/10.1186/s10020-018-0056-z
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