• Richard W Pierce, Veronika Shabanova, Michael Canarie, Mathew Pinto, Yong Sing da Silva, Vineet Bhandari, and John S Giuliano.
• Department of Pediatrics, Yale University, New Haven, Connecticut.
• Shock. 2019 Mar 1; 51 (3): 298-305.

ObjectiveAngiopoietins are postulated diagnostic biomarkers in children and adults with severe sepsis and septic shock. The diagnostic value of angiopoietins in children less than 5 years old has not been established, nor has their effect on permeability in the capillary microvasculature. We aim to determine if levels of angiopoietin-1 or -2 (angpt-1, -2) are diagnostic for severe sepsis/shock in young children and whether they affect the permeability of cultured human dermal microvascular endothelial cells (HDMEC).DesignProspective observational study of children < 5 years old. Patients were classified as non-systemic inflammatory response syndrome (SIRS), SIRS/sepsis and severe sepsis/septic shock.SettingTertiary care pediatric hospitals.PatientsCritically ill children.InterventionsNone.MeasurementsPlasma angpt-1 and -2 levels were measured with enzyme-linked immunoassays. Expression of angpt-2 in endothelial cells was assessed with quantitative polymerase chain reaction. Permeability changes in cultured HDMECs were assessed with transendothelial electrical resistance measurements.ResultsAngpt-1 levels were significantly higher in younger children compared with levels found in previous study of older children across disease severity (all P < 0.001). Angpt-2 was significantly higher in this cohort with severe sepsis/septic shock compared with children without SIRS and SIRS/sepsis (all P < 0.003). Angpt-2/1 ratio was also elevated in children with severe sepsis/septic shock but an order of magnitude less than older children (P < 0.02, P = 0.002). Angpt-1 and -2 did not affect basal HDMEC permeability or modulate leak in isolation or in the presence of tumor necrosis factor (TNF).ConclusionsAngpt-2 levels and the angpt-2/1 ratio are appropriate diagnostic biomarkers of severe sepsis/septic shock in children less than 5 years old. Neither angpt-1 nor -2 affects basal HDMEC permeability alone or modulates TNF induced capillary leak.

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