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. und Kreth, S. (2018): MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis. In: Molecular Medicine, Bd. 24

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-beta. 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1076-1551
• Sprache: Englisch