Circulating microtranscriptome profiles reveal distinct expression of microRNAs in severe leptospirosis

PLoS Negl Trop Dis. 2020 Nov 11;14(11):e0008809. doi: 10.1371/journal.pntd.0008809. eCollection 2020 Nov.

Abstract

Biomarkers to predict the severity of leptospirosis are still lacking. This study aimed to identify and validate microRNAs in patients with severe leptospirosis, that could potentially be used as biomarkers for predicting an unfavorable outcome. Serum samples were collected from participants with definite diagnosis of leptospirosis. The participants were divided into two groups, non-severe and severe leptospirosis, as defined by the Specific Organ Sequential Organ Failure (SOFA) Score of more than two in any organ. Microtranscriptome analysis was performed using the NanoString miRNA Expression Assay. The expression level of candidate miRNAs was then validated by quantitative RT-PCR. Based on the NanoString, the microtranscriptome profile of the severe group was significantly different from that of the non-severe group. Upregulation of miR155-5p, miR362-3p, miR502-5p, miR601, miR1323, and miR630 in the severe group were identified, and further investigated. A total of 119 participants were enrolled in the validation cohort. Serum miR155-5p and miR630 levels were significantly higher in the severe group compared to the non-severe group. The combined use of miR155-5p or miR-630 with serum bicarbonate levels had an AUC of 0.79 (95%CI; 0.69-0.89, p<0.001) in identifying the severity of the disease. This data provides the first evidence that the microtranscriptome profiles of patients with severe leptospirosis were different from the non-severe group. Serum miR155-5p and miR630 levels might be novel biomarkers for identifying severe leptospirosis.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood*
  • Female
  • Gene Expression Profiling
  • Humans
  • Leptospira / isolation & purification*
  • Leptospirosis / diagnosis*
  • Leptospirosis / pathology
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Middle Aged
  • Prospective Studies
  • Real-Time Polymerase Chain Reaction
  • Severity of Illness Index
  • Transcriptome / genetics

Substances

  • Biomarkers
  • MIRN155 microRNA, human
  • MicroRNAs

Grants and funding

This research project is supported by the Second Century Fund (C2F), Chulalongkorn University (Umaporn Limothai received the grant). Pisit Tangkijvanich received funding from The Thailand Research Fund (TRF) Senior Research Scholar (RTA6280004). Funding was also provided by the Center of Excellence in Hepatitis and Liver Cancer and Excellence Center for Critical Care Nephrology, Faculty of Medicine, Chulalongkorn University. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.