Proteomic biomarkers for early diagnosis and prognosis in pediatric sepsis

Table 3 Biomarkers characteristics

Biomarker/panel	Clinical context	Platform (discovery validation)	Threshold (per study)	AUC (95%CI)	Sens	Spec	Notes
Interleukin-27	Sepsis vs systemic inflammatory response syndrome (diagnostic)	Transcriptomics-driven discovery to serum immunoassay	≥ 5.0 ng/mL	0.811 (0.755-0.868)	0.61	0.92	“Rule-in” behavior; outperformed PCT; classification and regression tree with PCT improved prediction
HP (infants)	Prognosis (poor outcome)	TMT-LC-MS/MS to ELISA	Study-defined	0.875 (0.700-1.000)	0.83	1.00	Opposite directionality in toddlers; age-adapted use essential
THBS1 (infants)	Prognosis (poor outcome)	TMT-LC-MS/MS to ELISA	218.38 ng/mL	0.877 (0.701-1.000)	1.00	0.60	Infant-specific signal; not significant in toddlers
HP + THBS1 (infants, combined)	Prognosis (poor outcome)	TMT-LC-MS/MS to ELISA	Panel score	0.958 (0.868-1.000)	0.917	1.00	Best infant prognostic combo
Serum amyloid A 1	Sepsis vs healthy (diagnostic)	Label-free LC-MS to ELISA	35891 ng/mL (Youden)	0.978 (0.946-1.000)	0.889	1.00	Early rising acute-phase protein; split patients/controls cleanly
Soluble CD25	Sepsis vs healthy (diagnostic)	Label-free LC-MS to ELISA	3209 pg/mL (Youden)	0.970 (0.920-1.000)	0.946	1.00	Performed better than PCT in intensive care unit admission cohorts (cited by authors)
Leucine-rich alpha-2-glycoprotein 1	Sepsis vs healthy (diagnostic)	Label-free LC-MS to ELISA	56951.5 ng/mL (Youden)	0.933 (0.86-1.00)	0.867	0.89	Acute-phase-responsive glycoprotein; strong single-marker ROC
Slow off-rate modified aptamer (capture reagent) signature (multi-protein)	Sepsis vs post- cardiopulmonary bypass infection-negative systemic inflammation (diagnostic differentiation)	SOMAscan (aptamer-based high-plex proteomic platform) 1305-plex; linear models for microarray data + Benjamini-Hochberg false-discovery-rate correction, Boruta; weighted gene co-expression network analysis	-	-	-	-	111 differentially ex-pressed (proteins/genes) proteins (8.6% of panel); sepsis-correlated modules identified; no single-analyte ROC reported

AUC: Area under the receiver operating characteristic curve; CI: Confidence interval; ELISA: Enzyme-linked immunosorbent assays; HP: Haptoglobin; LC-MS/MS: Liquid chromatography-tandem mass spectrometry; PCT: Procalcitonin; THBS1: Thrombospondin 1; TMT: Tandem mass tags; ROC: Receiver operating characteristic.