Serum ceramide levels are altered in multiple sclerosis

Angeliki G. Filippatou, Mohammed Moniruzzaman, Elias S. Sotirchos, Kathryn C. Fitzgerald, Grigorios Kalaitzidis, Jeffrey Lambe, Eleni Vasileiou, Shiv Saidha, Jerry L. Prince, Norman Haughey, Peter A. Calabresi, Pavan Bhargava

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1506-1519
Number of pages14
JournalMultiple Sclerosis Journal
Issue number10
StatePublished - Sep 2021


  • Multiple sclerosis
  • ceramides
  • lipidomics

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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