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A Coordinated Adhesion-Molecule Activation Profile in Pediatric Sepsis: A Prospective Cohort Study from Vietnam
Bui Thanh Liem1,2, Chu Van Thien3, Nguyen Trong Nghia3
1Department of Pediatrics, School of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam.
Abstract:
Background/Objectives: Pediatric sepsis is increasingly recognized as a syndrome involving immune-vascular dysregulation. However, most pediatric biomarker studies focus on individual molecules rather than coordinated patterns of leukocyte-endothelial activation. This study aimed to evaluate whether children diagnosed with sepsis within 48 h of admission showed a coordinated soluble adhesion-molecule activation profile measured at enrollment. Methods: This prospective cohort study included 144 children aged 1-60 months with suspected infection enrolled at Dong Nai Children's Hospital, Vietnam, from May 2021 to October 2022. Blood samples were collected at enrollment. Sepsis was classified according to the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria within 48 h of admission. Twelve soluble adhesion molecules were measured using a multiplex immunoassay. A composite adhesion activation score was derived by log2 transformation, z-score standardization, and averaging across the 12 markers. Principal component analysis (PCA) was used as an exploratory method to summarize the shared variation across the adhesion-molecule panel. C-reactive protein (CRP) was included as a routinely available inflammatory comparator. Results: Among 144 children, 32 (22.2%) were diagnosed with sepsis within 48 h of admission. Individual marker discrimination was strongest for L-selectin (area under the receiver operating characteristic curve [AUC] 0.883), followed by soluble vascular cell adhesion molecule-1 (sVCAM-1; AUC 0.855), intercellular adhesion molecule-3 (ICAM-3; AUC 0.838), P-selectin glycoprotein ligand-1 (PSGL-1; AUC 0.836), E-selectin (AUC 0.819), and intercellular adhesion molecule-2 (ICAM-2; AUC 0.819). CRP also differed between children with and without sepsis but had a lower AUC than the leading adhesion molecules in descriptive ROC analyses. The composite adhesion activation score was strongly associated with sepsis (odds ratio 7.95 per 1-standard deviation increase; 95% confidence interval 3.44-18.40; p < 0.001) and showed good discrimination (AUC 0.855; 95% confidence interval 0.776-0.931). The first principal component explained 70.0% of biomarker variance, consistent with coordinated elevation of correlated adhesion molecules. Conclusions: In this prospective Vietnamese pediatric cohort, children diagnosed with sepsis within 48 h of admission showed coordinated elevation of soluble adhesion molecules measured at enrollment. These findings support the biological relevance of leukocyte-endothelial activation in pediatric sepsis. However, the adhesion-molecule activation profile should be considered exploratory and hypothesis-generating, requiring external validation and further evaluation against simplified, clinically feasible biomarker approaches.
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