Diagnosis and mortality prediction of sepsis via lysophosphatidylcholine 16:0 measured by MALDI-TOF MS

Abstract

Sepsis remains a critical problem with high mortality worldwide, but there is still a lack of reliable biomarkers. We aimed to evaluate the serum lysophosphatidylcholine (LPC) 16:0 as a biomarker of sepsis using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Patients admitted to intensive care unit at Severance Hospital from March 2017 through June 2018 were prospectively enrolled. The inclusion criteria were the fulfillment of at least two criteria of systemic inflammatory response syndrome (SIRS) or the presence of sepsis. Of the 127 patients, 14 had non-infectious SIRS, 41 had sepsis, and 72 had septic shock. The mean serum LPC 16:0 concentration (µmol/L) in non-infectious SIRS was significantly higher than in patients with sepsis and septic shock (101.1 vs. 48.92, p < 0.05; 101.1 vs. 25.88, p < 0.001, respectively). The area under the curve (AUC) predicting 28-day mortality using ΔLPC16:0 (D1-D0) levels was 0.7, which was comparable with the APACHE II score (AUC 0.692) and SOFA score (AUC 0.67). Mechanical ventilation, CRRT, lactate, Δ LPC16:0 (D1-D0) less than the cutoff value were significantly associated with 28-day mortality in multivariable analysis. Our results suggest that LPC16:0 could be a useful biomarker for sepsis diagnosis and mortality prediction in icU patients. Sepsis is a critical health problem and is one of the main causes of death in intensive care units (ICU) worldwide 1,2. Although the sepsis mortality rate has decreased recently, it is still estimated to be between 35 and 55% 3. As clinical information alone is rarely sufficient to detect sepsis, much effort has been expended to identify biomarkers for the early detection of sepsis, risk stratification, and prognostic prediction 4. C-reactive protein (CRP) and procalcitonin (PCT) have been widely studied as sepsis biomarkers 5,6 , but it remains difficult to differentiate sepsis from other non-infectious inflammatory diseases. Recent evidence suggests that cell surface markers associated with immune dysfunction 7,8 and a peripheral blood-based molecular assay, designated as "SeptiCyte LAB," could be promising for discriminating sepsis from non-infectious systemic inflammation 9,10. However, these approaches may require considerable time, effort, and cost. Since matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) was developed, it has been widely used for the analysis of peptides, whole proteins, and nucleotides. The advantages of MALDI-TOF MS compared to those of other analytical methods include easy sample preparation, sensitive detection (< fmol), wide detection range of up to 500 kDa, and short analysis time 11,12. In our previous study 12 , we identified differentially abundant low molecular weight molecules in the serum of healthy volunteers and sepsis patients using MALDI-TOF MS based on a parylene-matrix chip. The selected mass peaks of m/z (mass-to-charge) were 496.3 and 518.3 and tandem mass spectrometry was then performed

Understanding protection from SARS-CoV-2 using metabolomics

“…Another source of monolaurin could be from the degradation of lysophosphatidylcholine 12:0 (LPC12:0). Increased levels of LPCs were found in COVID-19 patients, while another study reported that decreased concentration of LPC16:0 could be a useful biomarker for sepsis diagnosis and mortality prediction in intensive care unit patients 34 .…”

Identification and characterization of lysophosphatidylcholine 14:0 as a biomarker for drug-induced lung disease

“…Consistently, we found that plasma LPC(14:0) concentrations were decreased in patients with BaPn. LPCs have also been proposed as useful biomarkers for diagnosing sepsis and predicting patient mortality 28 , while metabolomics and lipidomics screening have recently revealed decreased serum LPC levels in patients with COVID-19 with lung injury 29,30 . Our results further strengthen the association between blood LPC levels and acute inflammation.…”

Dysregulation of the Lysophosphatidylcholine/Autotaxin/Lysophosphatidic Acid Axis in Acute‐on‐Chronic Liver Failure Is Associated With Mortality and Systemic Inflammation by Lysophosphatidic Acid–Dependent Monocyte Activation

“…Respiratory and renal failure, together with the occurrence of sepsis, could be confounding factors. It may be that some alteration of specific LPCs (e.g., LPC 16:0) is driven by sepsis, ( 46 ) in addition to hepatic and nonhepatic modulation of the LPC‐ATX‐LPA axis. Our data demonstrate that monocytes themselves up‐regulate ATX/ENPP2 expression following LPS stimulation, which could alter the lipid profile of their immediate microenvironment.…”