Serum ceramide levels are altered in multiple sclerosis.

Tytuł:: Serum ceramide levels are altered in multiple sclerosis.
Autorzy:: Filippatou AG; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Moniruzzaman M; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sotirchos ES; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Fitzgerald KC; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kalaitzidis G; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lambe J; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Vasileiou E; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Saidha S; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Prince JL; Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD, USA.
Haughey N; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Calabresi PA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Bhargava P; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Źródło:: Multiple sclerosis (Houndmills, Basingstoke, England) [Mult Scler] 2021 Sep; Vol. 27 (10), pp. 1506-1519. Date of Electronic Publication: 2020 Dec 14.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: 2006- : London : SAGE Publications
Original Publication: Houndmills, Basingstoke, Hampshire, UK : Stockton Press, c1995-
MeSH Terms:: Multiple Sclerosis*
Ceramides ; Humans ; Retina ; Retinal Ganglion Cells ; Tomography, Optical Coherence
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Grant Information:: K01 MH121582 United States MH NIMH NIH HHS; R01 NS082347 United States NS NINDS NIH HHS
Contributed Indexing:: Keywords: Multiple sclerosis; ceramides; lipidomics
Substance Nomenclature:: 0 (Ceramides)
Entry Date(s):: Date Created: 20201214 Date Completed: 20211021 Latest Revision: 20221118
Update Code:: 20240104
PubMed Central ID:: PMC8200368
DOI:: 10.1177/1352458520971816
PMID:: 33307993
: Czasopismo naukowe

Background: Sphingolipids are myelin components and inflammatory signaling intermediates. Sphingolipid metabolism may be altered in people with multiple sclerosis (PwMS), but existing studies are limited by small sample sizes.
Objectives: To compare the levels of serum ceramides between PwMS and healthy controls (HCs) and to determine whether ceramide levels correlate with disability status, as well as optical coherence tomography (OCT)-derived rates of retinal layer atrophy.
Methods: We performed targeted lipidomics analyses for 45 ceramides in PwMS ( n = 251) and HCs ( n = 68). For a subset of PwMS, baseline and 5-year Expanded Disability Status Scale (EDSS) assessments ( n = 185), or baseline and serial spectral-domain OCT ( n = 180) were assessed.
Results: Several ceramides, including hexosylceramides, lactosylceramides, and dihydroceramides, were altered in PwMS compared with HCs. Higher levels of Cer16:0 were associated with higher odds of EDSS worsening at 5 years in univariable (odds ratio (OR) = 3.84, 95% confidence interval (CI) = 1.41-10.43) and multivariable analyses accounting for age, sex, and race (OR = 2.97, 95% CI = 1.03-8.59). Each 1 ng/mL higher concentration of Hex-Cer22:0 and DH-HexCer22:0 was associated with accelerated rates (μm/year) of ganglion cell + inner plexiform layer (-0.138 ± 0.053, p = 0.01; -0.158 ± 0.053, p = 0.003, respectively) and peripapillary retinal nerve fiber layer thinning (-0.305 ± 0.107, p = 0.004; -0.358 ± 0.106, p = 0.001, respectively).
Conclusion: Ceramide levels are altered in PwMS and may be associated with retinal neurodegeneration and physical disability.

Comment in: Mult Scler. 2022 Nov;28(13):2147-2148. (PMID: 35369786)
Comment in: Mult Scler. 2022 Nov;28(13):2148-2149. (PMID: 35369796)

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