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; Jocelyn R Grunwell; Dominic Sanfilippo; Jeremy W Prokop; Todd A Lydic; Surender Rajasekaran

doi:10.3390/jpm11050339

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

J Pers Med. 2021 Apr 24;11(5):339. doi: 10.3390/jpm11050339.

Authors

Mara Leimanis-Laurens^{1

2}, Emily Wolfrum³, Karen Ferguson¹, Jocelyn R Grunwell⁴, Dominic Sanfilippo^{1

2}, Jeremy W Prokop^{2

5}, Todd A Lydic⁶, Surender Rajasekaran^{1

2

7}

Affiliations

¹ Pediatric Critical Care Unit, Helen DeVos Children's Hospital, Grand Rapids, MI 49503, USA.
² Department of Pediatric and Human Development, College of Human Medicine, Michigan State University, Life Sciences Bldg. 1355 Bogue Street, East Lansing, MI 48824, USA.
³ Bioinformatics & Biostatistics Core, Van Andel Institute, Grand Rapids, MI 49503, USA.
⁴ Pediatric Critical Care Medicine, Emory University & Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.
⁵ Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA.
⁶ Collaborative Mass Spectrometry Core, Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
⁷ Office of Research, Spectrum Health, Grand Rapids, MI 49503, USA.

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.

Keywords: critical illness; glycerolipids; glycerophosphatidylcholine; lipidomics; multi-organ dysfunction syndrome; pediatrics; sphingolipids; sphingomyelin.

Abstract

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