Biomarkers of sepsis and their potential value in diagnosis, prognosis and treatment

Abstract

Biomarkers have great potential to improve the diagnosis and treatment of sepsis. The available literature supports the potential utility of sTREM-1, IL-27, suPAR, neutrophil CD64, presepsin, cfDNA and miRNAs as novel diagnostic, prognostic and treatment response biomarkers. The future of sepsis biomarkers lies in extensive validation studies of such novel biomarkers across heterogeneous populations and exploration of their power in combination. Furthermore, the use of a companion diagnostics model may augment the ability of investigators to identify novel sepsis biomarkers and develop specific therapeutic strategies based on biomarker information.

Keywords::

• biomarker
• cfDNA
• combination biomarkers
• companion diagnostics
• IL-27
• miRNA
• neutrophil CD64
• presepsin
• sepsis
• suPAR
• TREM-1

Financial & competing interests disclosure

The authors were supported by NIH Grants RO1GM064619, RO1GM099773 and R01GM108025. HR Wong and the Cincinnati Children’s Hospital Research Foundation have submitted patent applications for the use of IL-27 as a sepsis diagnostic biomarker and for PERSEVERE. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Sepsis biomarkers have potential to alter the timeliness of diagnosis and improve management by providing prognostic information to clinicians in real-time.

• Soluble form of triggering receptor expressed on myeloid cells-1 has diagnostic potential as a sepsis biomarker, but further validation studies are necessary before regular use. Exploration comparing serum versus site-specific levels may be useful to improve bedside utility.

• IL-27 may be useful diagnostic sepsis biomarker in pediatric patients, but does not produce similar general results in adult studies.

• Soluble urokinase-type plasminogen activator receptor is a useful prognostic sepsis biomarker, but further studies to validate cutoff levels to predict mortality are needed.

• Neutrophil CD64 is a promising diagnostic and prognostic sepsis biomarker, but more studies that are robust would be useful to further evaluate its potential.

• Presepsin is a promising sepsis biomarker with a sound body of research to confirm its diagnostic and prognostic utility. Further studies are needed to validate cut-off values before it can be clinically utilized.

• Cell-free plasma DNA and miRNAs are largely unexplored targets that may offer a new realm of sepsis biomarker investigation.

• Combination biomarkers have perhaps the best potential to provide highly sensitive and specific real-time results to influence bedside diagnostic and therapeutic decisions.

• Companion diagnostics offer a previously unutilized method for identifying sepsis biomarkers and developing therapeutic strategies based on biomarker information.