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Association of arachidonic acid-derived lipid mediators with disease severity in patients with relapsing and progressive multiple sclerosis
Excessive activation of certain lipid mediator (LM) pathways plays a role in the complex
pathogenesis of multiple sclerosis (MS). However, the relationship between bioactive LMs and
different aspects of CNS-related pathophysiologic processes remains largely unknown.
Therefore, in this study, we assessed the association of bioactive LMs belonging to the ω-3/ω-6
lipid classes with clinical and biochemical (serum neurofilament light [sNfL] and serum glial
fibrillary acidic protein [sGFAP]) parameters and MRI-based brain volumes in patients with
MS (PwMS) and healthy controls (HCs).
Methods
A targeted high-performance liquid chromatography-tandem mass spectrometry approach was used
on plasma samples of PwMS and HCs of the Project Y cohort, a cross-sectional population-based
cohort that contains PwMS all born in 1966 in the Netherlands and age-matched HCs. LMs were
compared between PwMS and HCs and were correlated with...Show moreBackground and Objectives
Excessive activation of certain lipid mediator (LM) pathways plays a role in the complex
pathogenesis of multiple sclerosis (MS). However, the relationship between bioactive LMs and
different aspects of CNS-related pathophysiologic processes remains largely unknown.
Therefore, in this study, we assessed the association of bioactive LMs belonging to the ω-3/ω-6
lipid classes with clinical and biochemical (serum neurofilament light [sNfL] and serum glial
fibrillary acidic protein [sGFAP]) parameters and MRI-based brain volumes in patients with
MS (PwMS) and healthy controls (HCs).
Methods
A targeted high-performance liquid chromatography-tandem mass spectrometry approach was used
on plasma samples of PwMS and HCs of the Project Y cohort, a cross-sectional population-based
cohort that contains PwMS all born in 1966 in the Netherlands and age-matched HCs. LMs were
compared between PwMS and HCs and were correlated with levels of sNfL, sGFAP, disability
(Expanded Disability Status Scale [EDSS]), and brain volumes. Finally, significant correlates were
included in a backward multivariate regression model to identify which LMs best related to disability.
Results
The study sample consisted of 170 patients with relapsing remitting MS (RRMS), 115 patients
with progressive MS (PMS), and 125 HCs. LM profiles of patients with PMS significantly differed
from those of patients with RRMS and HCs, particularly patients with PMS showed elevated
levels of several arachidonic acid (AA) derivatives. In particular, 15-hydroxyeicosatetraenoic acid
(HETE) (r = 0.24, p < 0.001) correlated (average r = 0.2, p < 0.05) with clinical and biochemical
parameters such as EDSS and sNfL. In addition, higher 15-HETE levels were related to lower
total brain (r = −0.24, p = 0.04) and deep gray matter volumes (r = −0.27, p = 0.02) in patients
with PMS and higher lesion volume (r = 0.15, p = 0.03) in all PwMS.
Discussion
In PwMS of the same birth year, we show that ω-3 and ω-6 LMs are associated with disability,
biochemical parameters (sNfL, GFAP), and MRI measures. Furthermore, our findings indicate
that, particularly, in patients with PMS, elevated levels of specific products of the AA pathway,
such as 15-HETE, associate with neurodegenerative processes. Our findings highlight the
potential relevance of ω-6 LMs in the pathogenesis of MS.
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- All authors
- Broos, J.Y.; Loonstra, F.C.; Ruiter, L.R.J. de; Gouda, M.; Fung, W.H.; Schoonheim, M.M.; Heijink, M.; Strijbis, E.M.M.; Teunissen, C.; Killestein, J.; Vries, H.E. de; Giera, M.; Uitdehaag, B.M.J.; Kooij, G.
- Date
- 2023-08-01
- Journal
- Neurology
- Volume
- 101
- Issue
- 5
- Pages
- e533 - e545