TY - JOUR
TI - MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis
AU - Möhnle, P.
AU - Hirschberger, S.
AU - Hinske, L.C.
AU - Briegel, J.
AU - Hübner, M.
AU - Weis, S.
AU - Dimopoulos, G.
AU - Bauer, M.
AU - Giamarellos-Bourboulis, E.J.
AU - Kreth, S.
JO - Current Molecular Medicine
PY - 2018
VL - 24
TODO - 1
SP - null
PB - BioMed Central Ltd.
SN - 1566-5240
TODO - 10.1186/s10020-018-0056-z
TODO - 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
TODO - 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).
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