Diagnostic potential of circulating cell-free microRNAs for community-acquired pneumonia and pneumonia-related sepsis

Stefanie Hermann1, Florian Brandes2, Benedikt Kirchner1

  • 1Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany.

Insights

Cell-free microRNAs (miRNAs) in extracellular vesicles show promise as biomarkers for community-acquired pneumonia (CAP) and sepsis. These findings could aid in early detection and intervention for patients at risk of severe complications.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genomics

Background:

  • Cell-free microRNAs (miRNAs) are implicated in disease pathogenesis and can be packaged into extracellular vesicles (EVs).
  • Investigating circulating miRNAs as biomarkers for inflammatory lung diseases like community-acquired pneumonia (CAP) and sepsis is crucial for early diagnosis and treatment.

Purpose of the Study:

  • To evaluate the potential of cell-free miRNAs within EVs as diagnostic biomarkers for CAP and sepsis.
  • To identify specific miRNA signatures that can differentiate between healthy individuals, CAP patients, and sepsis patients.

Main Methods:

  • Serum extracellular vesicles (EVs) were isolated from healthy volunteers, CAP patients, and sepsis patients.
  • Small RNA profiling was performed using next-generation sequencing (NGS), followed by multivariate analysis.
  • Candidate biomarker miRNAs were validated using reverse transcription quantitative real-time PCR (RT-qPCR).

Main Results:

  • Differential gene expression analysis identified 29 differentially expressed miRNAs in CAP versus volunteers and 25 in CAP versus sepsis.
  • A signature of 12 miRNAs was identified using sparse partial least discriminant analysis.
  • Three miRNAs (miR-1246, miR-193a-5p, and miR-542-3p) emerged as significant biomarkers, with miR-1246 correlating with disease severity.

Conclusions:

  • Cell-free miRNAs encapsulated in EVs represent potential novel biomarkers for CAP.
  • These miRNA biomarkers may facilitate the early identification of patients progressing to sepsis, enabling timely therapeutic interventions.