Dataset Information

Biological Activity of Masked Endotoxin.

ABSTRACT: Low endotoxin recovery (LER) is a recently discovered phenomenon describing the inability of limulus amebocyte lysate (LAL)-based assays to detect lipopolysaccharide (LPS) because of a "masking effect" caused by chelators or detergents commonly used in buffer formulations for medical products and recombinant proteins. This study investigates the masking capacities of different buffer formulations and whether masked endotoxin is biologically active. We show that both naturally occurring endotoxin as well as control standard endotoxin can be affected by LER. Furthermore, whereas masked endotoxin cannot be detected in Factor C based assays, it is still detectable in a cell-based TLR4-NF-?B-luciferase reporter gene assay. Moreover, in primary human monocytes, masked LPS induces the expression of pro-inflammatory cytokines and surface activation markers even at very low concentrations. We therefore conclude that masked LPS is a potent trigger of immune responses, which emphasizes the potential danger of masked LPS, as it may pose a health threat in pharmaceutical products or compromise experimental results.

SUBMITTER: Schwarz H

PROVIDER: S-EPMC5357793 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Biological Activity of Masked Endotoxin.

Schwarz Harald H Gornicec Jan J Neuper Theresa T Parigiani Maria Alejandra MA Wallner Michael M Duschl Albert A Horejs-Hoeck Jutta J

Scientific reports 20170320

Low endotoxin recovery (LER) is a recently discovered phenomenon describing the inability of limulus amebocyte lysate (LAL)-based assays to detect lipopolysaccharide (LPS) because of a "masking effect" caused by chelators or detergents commonly used in buffer formulations for medical products and recombinant proteins. This study investigates the masking capacities of different buffer formulations and whether masked endotoxin is biologically active. We show that both naturally occurring endotoxin ...[more]

PMID: 28317862

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Project description:Background: Extracorporeal membrane oxygenation (ECMO) life support has become an integral part of intensive care. The endotoxin activity assay (EAA) is a useful test to measure endotoxemia severity in whole blood. To date, no information is available regarding the EAA levels and their effect on clinical outcomes in critically ill patients with ECMO support. Methods: This prospective observational pilot study enrolled adult critically ill patients with ECMO support from August 2019 to December 2020. The EAA levels were measured within 24 h (T1), and at 25-48 (T2), 49-72 (T3), and 73-96 h (T4) after ECMO initiation. This study primarily aimed to investigate the incidence of high EAA levels (≥0.6) at each time point. Subsequent exploratory analyses were conducted to compare the EAA levels of venoarterial ECMO (VA-ECMO) patients between 30-day survivors and non-survivors. Post-hoc analysis was performed to compare the clinical outcomes of VA-ECMO patients with elevated EAA levels at T3 (vs. T1) and those without elevated EAA levels. Results: A total of 39 VA-ECMO patients and 15 venovenous ECMO (VV-ECMO) patients were enrolled. At T1, the incidence of high EAA level (≥0.6) was 42% in VV-ECMO patients and 9% in VA-ECMO patients (P = 0.02). At T2, the incidence of high EAA level was 40% in VV-ECMO patients and 5% in VA-ECMO patients (P = 0.005). In VA-ECMO patients, EAA levels at T3 were significantly higher in 30-day non-survivors than in survivors (median [interquartile range]: 0.49 [0.37-0.93] vs. 0.31 [0.19-0.51], median difference 0.16 [95% confidence interval [CI], 0.02-0.31]; P = 0.024). Moreover, VA-ECMO patients with elevated EAA levels at T3 (vs. T1) had lower 30-day survival than patients without elevated EAA levels (39 vs. 83%, P = 0.026) and fewer ECMO free days by day 30 (median: 3 vs. 23 days, median difference 12 days [95% CI, 0-22]; P = 0.028). Conclusions: A certain proportion of patients experienced high EAA levels (≥0.6) after VV-ECMO or VA-ECMO initiation. VA-ECMO patients with an elevated EAA level at 49-72 h were associated with poor clinical outcomes.

Dataset Information

Biological Activity of Masked Endotoxin.

Publications

Biological Activity of Masked Endotoxin.

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