Source: Journal of Translational Medicine
Vol 19, #1, p 370.
Date: August 28, 2021
Sex-specific plasma lipid profiles of ME/CFS patients and their
association with pain, fatigue, and cognitive symptoms
Aurore Nkiliza(1,2,*), Megan Parks(3,4), Adam Cseresznye(3,4), Sarah
Oberlin(3,4), James E Evans(3,4), Teresa Darcey(3,4), Kristina
Aenlle(5), Daniel Niedospial(3,4), Michael Mullan(3,4), Fiona
Crawford(3,4), Nancy Klimas(5), Laila Abdullah(3,4)
1 Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, 34243, USA.
2 James A. Haley Veterans' Hospital, 2040 Whitfield Ave, Tampa, FL, USA.
3 Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, 34243, USA.
4 James A. Haley Veterans' Hospital, 2040 Whitfield Ave, Tampa, FL, USA.
5 Institute for NeuroImmune Medicine, VAMC, GRECC, Nova Southeastern
University, Miami, USA.
* Corresponding author. Email: anki...@roskampinstitute.org
Received 24 April 2021
Accepted 09 August 2021
Published 28 August 2021
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex
illness which disproportionally affects females. This illness is
associated with immune and metabolic perturbations that may be
influenced by lipid metabolism. We therefore hypothesized that plasma
lipids from ME/CFS patients will provide a unique biomarker signature of
disturbances in immune, inflammation and metabolic processes associated
Lipidomic analyses were performed on plasma from a cohort of 50 ME/CFS
patients and 50 controls (50% males and similar age and ethnicity per
group). Analyses were conducted with nano-flow liquid chromatography
(nLC) and high-performance liquid chromatography (HPLC) systems coupled
with a high mass accuracy ORBITRAP mass spectrometer, allowing detection
of plasma lipid concentration ranges over three orders of magnitude. We
examined plasma phospholipids (PL), neutral lipids (NL) and bioactive
lipids in ME/CFS patients and controls and examined the influence of sex
on the relationship between lipids and ME/CFS diagnosis.
Among females, levels of total phosphatidylethanolamine (PE), omega-6
arachidonic acid-containing PE, and total hexosylceramides (HexCer) were
significantly decreased in ME/CFS compared to controls. In males, levels
of total HexCer, monounsaturated PE, phosphatidylinositol (PI), and
saturated triglycerides (TG) were increased in ME/CFS patients compared
to controls. Additionally, omega-6 linoleic acid-derived oxylipins were
significantly increased in male ME/CFS patients versus male controls.
Principal component analysis (PCA) identified three major components
containing mostly PC and a few PE, PI and SM species-all of which were
negatively associated with headache and fatigue severity, irrespective
of sex. Correlations of oxylipins, ethanolamides and ME/CFS symptom
severity showed that lower concentrations of these lipids corresponded
with an increase in the severity of headaches, fatigue and cognitive
difficulties and that this association was influenced by sex.
The observed sex-specific pattern of dysregulated PL, NL, HexCer and
oxylipins in ME/CFS patients suggests a possible role of these lipids in
promoting immune dysfunction and inflammation which may be among the
underlying factors driving the clinical presentation of fatigue, chronic
pain, and cognitive difficulties in ill patients. Further evaluation of
lipid metabolism pathways is warranted to better understand ME/CFS
Keywords: Myalgic encephalomyelitis/chronic fatigue syndrome, Lipidomic,
(c) 2021 BioMed Central Ltd.