Τίτλος:
MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2018 The Author(s).
Συγγραφείς:
Möhnle, P.
Hirschberger, S.
Hinske, L.C.
Briegel, J.
Hübner, M.
Weis, S.
Dimopoulos, G.
Bauer, M.
Giamarellos-Bourboulis, E.J.
Kreth, S.
Περιοδικό:
Current Molecular Medicine
Εκδότης:
BioMed Central Ltd.
Λέξεις-κλειδιά:
inducible T cell costimulator; interleukin 10; interleukin 2; interleukin 4; interleukin 7 receptor; microRNA; microRNA 143; microRNA 150; microRNA 15a; microRNA 16; microRNA 223; miR 342; miR 424; miR 93; transforming growth factor beta; unclassified drug; cytokine; microRNA; MIRN143 microRNA, human; MIRN150 microRNA, human, aged; Article; clinical article; controlled study; female; human; human cell; male; pilot study; polymerase chain reaction; priority journal; receiver operating characteristic; sepsis; septic shock; Sequential Organ Failure Assessment Score; T lymphocyte; adult; blood; genetics; immunology; middle aged; sepsis; T lymphocyte; very elderly, Adult; Aged; Aged, 80 and over; Cytokines; Female; Humans; Male; MicroRNAs; Middle Aged; Sepsis; T-Lymphocytes
DOI:
10.1186/s10020-018-0056-z
