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

• Main Authors: P Möhnle, S Hirschberger, L C Hinske, J Briegel, M Hübner, S Weis, G Dimopoulos, M Bauer, E J Giamarellos-Bourboulis, S Kreth
• Format: Article
• Language: English
• Published: BMC 2018-10-01
• Series: Molecular Medicine
• Subjects: Sepsis; Immunoparalysis; T-cells; T cell exhaustion; miRNA; Biomarker
• Online Access: http://link.springer.com/article/10.1186/s10020-018-0056-z

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.