Utility of Presepsin in Children Sepsis

Sepsis Syndrome

Presepsin (formerly CD14), is a glycoprotein receptor occurring at the surface of monocytes/macrophages. CD14 binds to lipopolysaccharide (LPS) complexes and LPS binding protein (LPB), which triggers the activation of toll-like receptor 4 (TLR4), resulting in the production of numerous pro-inflammatory cytokines. Following Presepsin activation by bacterial products, the CD14 complex is released in the circulation as its soluble form (sCD14), which in turn is cleaved by a plasma protease to generate a sCD14 fragment called sCD14-subtype (sCD14- ST). Plasma levels of sCD14 can be measured using an automated chemo-luminescent assay (PATHFAST).

Severe sepsis and septic shock represent major challenges of modern intensive care medicine, and still recently published international guidelines demand ongoing research about the pathophysiology, diagnostics and treatment. Currently, the diagnosis of sepsis is based on the presence of systemic inflammatory response syndrome (SIRS) criteria in the presence of a known infection. However, non-infectious SIRS associated with acute tissue injury and innate immune activation can induce clinical syndromes analogous to sepsis, including multiple trauma, pancreatitis, burns, and autoimmune diseases. Within the field of infectious diseases, a biomarker may be used for identifying a high risk group or predisposing condition, as an aid to identification of the disease, or to direct therapy and stratify patients according to their specific risk factors, and/or as an aid to therapeutic management in order to avoid relapse of infection. Within the recent years, dozens of potential biomarkers of infection have been described. The diagnostic performance of biomarkers is usually measured in terms of sensitivity, specificity, and by likelihood ratios and area under the ROC (Receiver Operating Characteristics) curves. Recently, several researches devolved their interest in discovering pathways involved in the innate immunity. Mediators involved in the recognition and elimination of bacterial endotoxins have been identified as new candidate biomarkers of sepsis, namely lipopolysaccharide binding protein (LBP) and soluble fractions of the membrane cluster of differentiation 14 (mCD14). Membrane CD14 is a multifunctional glycosylphosphatidylinositol-anchored membrane protein (cell surface glycoprotein), constitutively expressed by various cells, including monocytes, macrophages, neutrophils, etc. CD14 is a pattern recognition receptor for bacterial molecules, namely lipopolysaccharides (LPS) from Gram-negative bacteria and peptidoglycans together with lipoteichoic acid from Gram-positive bacteria. CD14 is crucial in activating the toll-like receptor 4 (TLR4)-specific proinflammatory signaling cascade and ultimately, initiating the inflammatory reaction against invading microorganisms. In the course of inflammatory reaction, plasma protease activity generates soluble CD14 fragments (sCD14), presepsin.

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