Hexosylceramides and Glycerophosphatidylcholine GPC(36:1) Increase in Multi-Organ Dysfunction Syndrome Patients with Pediatric Intensive Care Unit Admission over 8-Day Hospitalization.

Mara Leimanis-Laurens,Emily Wolfrum,Karen Ferguson,Surender Rajasekaran,Jeremy W Prokop,Jocelyn R Grunwell,Dominic Sanfilippo,Todd A Lydic

doi:10.3390/jpm11050339

Abstract

Glycero- and sphingo-lipids are important in plasma membrane structure, caloric storage and signaling. An un-targeted lipidomics approach for a cohort of critically ill pediatric intensive care unit (PICU) patients undergoing multi-organ dysfunction syndrome (MODS) was compared to sedation controls. After IRB approval, patients meeting the criteria for MODS were screened, consented (n = 24), and blood samples were collected from the PICU at HDVCH, Michigan; eight patients needed veno-arterial extracorporeal membrane oxygenation (VA ECMO). Sedation controls were presenting for routine sedation (n = 4). Plasma lipid profiles were determined by nano-electrospray (nESI) direct infusion high resolution/accurate mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Biostatistics analysis was performed using R v 3.6.0. Sixty-one patient samples over three time points revealed a ceramide metabolite, hexosylceramide (Hex-Cer) was high across all time points (mean 1.63–3.19%; vs. controls 0.22%). Fourteen species statistically differentiated from sedation controls (p-value ≤ 0.05); sphingomyelin (SM) [SM(d18:1/23:0), SM(d18:1/22:0), SM(d18:1/23:1), SM(d18:1/21:0), SM(d18:1/24:0)]; and glycerophosphotidylcholine (GPC) [GPC(36:01), GPC(18:00), GPC(O:34:02), GPC(18:02), GPC(38:05), GPC(O:34:03), GPC(16:00), GPC(40:05), GPC(O:36:03)]. Hex-Cer has been shown to be involved in viral infection and may be at play during acute illness. GPC(36:01) was elevated in all MODS patients at all time points and is associated with inflammation and brain injury.

Highlights

The human plasma lipidome has been well described in the last decade [1] with the launch of the Lipid Maps Consortium
We note a low abundance of sphingolipids and sphingomyelins for this cohort of critically ill pediatric patients
Trace amounts of markers that are pro-apoptotic and associated with membrane homeostasis were found

Summary

Introduction

The human plasma lipidome has been well described in the last decade [1] with the launch of the Lipid Maps Consortium (www.lipidmaps.org). Thousands [2], half of which consists of glycerolipids, glycerophospholipids and sphingolipids All of these lipid classes are structurally constituted of a fatty acid with long hydrocarbon chains, and a glycerol group, with sphingolipids as the only exception lacking a glycerol group (from Quehenberger and Dennis [1]). MODS depends largely on the critical illness diagnosis, the etiology of which may include sepsis, chronic diseases, and patients’ age (neonates at highest risk). Both proinflammatory and anti-inflammatory mediators play a role, for which the lungs are often the first organ affected (heart, brain, kidney, and liver as additional organs affected). Clinical presentations of pediatric MODS conditions include thrombocytopenia-associated multiple organ failure, hemophagocytic lymphohistiocytosis, Kawasaki syndrome, and hematologic malignancies

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Conclusion