Frontiers in immunology · 2026
Point-of-care LPS-induced TNF-α release testing for early sepsis risk stratification in the emergency department.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Cisteró Berta, Ceccato Adrian, Plata-Menchaca Erika P, Monforte Veronica, Caus-Capdevila Queralt, Areny-Balaguero Aina, Campaña-Duel Elena, Camprubí-Rimblas Marta, Goma-Fernandez Gemma, Guijarro Carla, Salom Patricia, Lopez Monica, Tajan Juan, Teles De Castro Tiago, Roman Vanessa, Vieyra Joan, Cubedo Judit, Guerrero Eduard, Gené Emilio, Artigas Antonio, Hernández-Jiménez Enrique
Аннотация
BACKGROUND AND OBJECTIVE: Early changes in innate immune responsiveness precede overt organ dysfunction in sepsis. In emergency department (ED) patients with suspected infection and physiological deterioration, we estimated the prevalence of reduced LPS-induced TNF-α responsiveness, characterized the associated clinical outcomes, and assessed the diagnostic accuracy of a point-of-care LPS-induced TNF-α release assay (TARA) for Sepsis-3 adjudicated at 24 h.
METHODS: In this prospective observational cohort, adults with suspected infection and NEWS2 ≥3 were consecutively enrolled. Whole-blood samples collected at ED arrival (0 h) and 4 h later were stimulated ex vivo with LPS, and TNF-α release was measured using the TARA assay.
RESULTS: Of the 203 enrolled patients, 180 had valid paired TARA results and 142 fulfilled Sepsis-3 criteria within 24 h. Reduced LPS-induced TNF-α responsiveness, defined by a negative TARA result, was frequent (75%) and was associated with higher Sepsis-3 adjudication (83.0% vs. 66.7%). Using a parallel rule (0 or 4 h), negative TARA identified Sepsis-3 with 78.9% sensitivity (95% CI 71.4 to 84.8), 39.5% specificity (95% CI 25.6 to 55.3), 83.0% PPV, 33.3% NPV, LR+ of 1.30, LR- of 0.54, and 70.6% accuracy. Predictive values are prevalence-dependent and not transportable to unselected ED populations, whereas the likelihood ratios are. In prespecified low-risk subsets, sensitivity was 87.0% (95% CI 75.6 to 93.6) with NEWS2 <5 and 79.1% (70.8 to 85.6) with qSOFA ≤1. Using a composite endpoint (Sepsis-2/Sepsis-3), accuracy improved to 77.0% with maintained sensitivity (78.8%). In a parsimonious model adjusted for age and qSOFA, TARA remained independently associated with Sepsis-3 (adjusted OR 2.94, 95% CI 1.28 to 6.75; p = 0.011), with an optimism-corrected AUC of 0.729 after bootstrap internal validation.
CONCLUSIONS: In ED patients with suspected infection and NEWS2 ≥3, point-of-care TARA identified a prevalent phenotype of reduced LPS-induced TNF-α responsiveness, with high sensitivity and low specificity for Sepsis-3, including in patients with low severity scores. This profile is consistent with an adjunctive rather than a stand-alone diagnostic role, requiring further confirmation in multicenter cohorts with broader ED case-mix.
METHODS: In this prospective observational cohort, adults with suspected infection and NEWS2 ≥3 were consecutively enrolled. Whole-blood samples collected at ED arrival (0 h) and 4 h later were stimulated ex vivo with LPS, and TNF-α release was measured using the TARA assay.
RESULTS: Of the 203 enrolled patients, 180 had valid paired TARA results and 142 fulfilled Sepsis-3 criteria within 24 h. Reduced LPS-induced TNF-α responsiveness, defined by a negative TARA result, was frequent (75%) and was associated with higher Sepsis-3 adjudication (83.0% vs. 66.7%). Using a parallel rule (0 or 4 h), negative TARA identified Sepsis-3 with 78.9% sensitivity (95% CI 71.4 to 84.8), 39.5% specificity (95% CI 25.6 to 55.3), 83.0% PPV, 33.3% NPV, LR+ of 1.30, LR- of 0.54, and 70.6% accuracy. Predictive values are prevalence-dependent and not transportable to unselected ED populations, whereas the likelihood ratios are. In prespecified low-risk subsets, sensitivity was 87.0% (95% CI 75.6 to 93.6) with NEWS2 <5 and 79.1% (70.8 to 85.6) with qSOFA ≤1. Using a composite endpoint (Sepsis-2/Sepsis-3), accuracy improved to 77.0% with maintained sensitivity (78.8%). In a parsimonious model adjusted for age and qSOFA, TARA remained independently associated with Sepsis-3 (adjusted OR 2.94, 95% CI 1.28 to 6.75; p = 0.011), with an optimism-corrected AUC of 0.729 after bootstrap internal validation.
CONCLUSIONS: In ED patients with suspected infection and NEWS2 ≥3, point-of-care TARA identified a prevalent phenotype of reduced LPS-induced TNF-α responsiveness, with high sensitivity and low specificity for Sepsis-3, including in patients with low severity scores. This profile is consistent with an adjunctive rather than a stand-alone diagnostic role, requiring further confirmation in multicenter cohorts with broader ED case-mix.