J. Pers. Med. 2021, 11, 339. https://doi.org/10.3390/jpm11050339 www.mdpi.com/journal/jpm Article 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 1,2, *, Emily Wolfrum 3 , Karen Ferguson 1 , Jocelyn R. Grunwell 4 , Dominic Sanfilippo 1,2 , Jeremy W. Prokop 2,5 , Todd A. Lydic 6 and Surender Rajasekaran 1,2,7 1 Pediatric Critical Care Unit, Helen DeVos Children’s Hospital, Grand Rapids, MI 49503, USA; karen.ferguson@spectrumhealth.org (K.F.); dominic.sanfilippo@helendevoschildrens.org (D.S.); surender.rajasekaran@spectrumhealth.org (S.R.) 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; prokopje@msu.edu 3 Bioinformatics & Biostatistics Core, Van Andel Institute, Grand Rapids, MI 49503, USA; Emily.Wolfrum@vai.org 4 Pediatric Critical Care Medicine, Emory University & Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA; jgrunwe@emory.edu 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; lydictod@msu.edu 7 Office of Research, Spectrum Health, Grand Rapids, MI 49503, USA * Correspondence: mara.leimanis@spectrumhealth.org; Tel.: +1-616-267-0106 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 con- trols 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 dif- ferentiated 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: lipidomics; pediatrics; critical illness; multi-organ dysfunction syndrome; glycerolipids; glycerophosphatidylcholine; sphingolipids; sphingomyelin 1. 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). From this work, it was Citation: Leimanis-Laurens, M.; Wolfrum, E.; Ferguson, K.; Grunwell, J.R.; Sanfilippo, D.; Prokop, J.W.; Lydic, T.A.; Rajasekaran, S. 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, 11, 339. https://doi.org/10.3390/ jpm11050339 Academic Editor: Laura Ruggeri Received: 16 February 2021 Accepted: 21 April 2021 Published: 24 April 2021 Publisher’s Note: MDPI stays neu- tral with regard to jurisdictional claims in published maps and insti- tutional affiliations. Copyright: © 2021 by the author. Li- censee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and con- ditions of the Creative Commons At- tribution (CC BY) license (http://cre- ativecommons.org/licenses/by/4.0/).