Synergistic impact of innate immunity hyper-activation and endothelial dysfunction on the magnitude of organ failure in the infection-sepsis continuum

Abstract

Biomarkers; Infection; Synergy

Biomarcadors; Infecció; Sinergia

Biomarcadores; Infección; Sinergia

Objectives Identifying host response biomarkers implicated in the emergence of organ failure during infection is key to improving the early detection of this complication. Methods Twenty biomarkers of innate immunity, T-cell response, endothelial dysfunction, coagulation, and immunosuppression were profiled in 180 surgical patients with infections of diverse severity (IDS) and 53 with no infection (nIDS). Those better differentiating IDS/nIDS in the area under the curve were combined to test their association with the sequential organ failure assessment score by linear regression analysis in IDS. Results were validated in another IDS cohort of 174 patients. Results C-reactive protein, procalcitonin, pentraxin-3, lipocalin-2 (LCN2), tumoral necrosis factor-α, angiopoietin-2, triggering receptor expressed on myeloid cells-1 (TREM-1) and interleukin (IL)-15 yielded an area under the curve ≥0.75 to differentiate IDS from nIDS. The combination of LCN2, IL-15, TREM-1, angiopoietin-2 (Dys-4) showed the strongest association with sequential organ failure assessment score in IDS (adjusted regression coefficient; standard error; P): Dys-4 (3.55;0.44; <0.001), LCN2 (2.24; 0.28; <0.001), angiopoietin-2 (1.92; 0.33; <0.001), IL-15 (1.78; 0.40; <0.001), TREM-1(1.74; 0.46; <0.001), tumoral necrosis factor-α (1.60; 0.31; <0.001), pentraxin-3 (1.12; 0.18; <0.001), procalcitonin (0.85; 0.12; <0.001). Dys-4 provided similar results in the validation cohort. Conclusions There is a synergistic impact of innate immunity hyper-activation (LCN2, IL-15, TREM-1) and endothelial dysfunction (angiopoietin-2) on the magnitude of organ failure during infection.

This work was supported by the Instituto de Salud Carlos III (ISCIII) and co-funded by European Regional Development Fund/European Social Fund “A way to make Europe“/”Investing in your future” [Project “PI19/00590” (JFBM), Project “PI22/00968” (JFBM), Sara Borrell program “CD018/0123” (APT) and PFIS program “FI20/00278” (AdlF)]. The funding sources did not play any role in the design of the study and collection, analysis, interpretation of data, or writing the manuscript.