Serum ceramide levels are altered in multiple sclerosis

Abstract

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.

Sex-specific plasma lipid profiles of ME/CFS patients and their association with pain, fatigue, and cognitive symptoms

“…Similarly, Cer did not reach significance in our current study, despite a generalized increase of about 18% in female ME/CFS patients compared to female controls. This contrasts with the study by Germain and colleagues [ 48 , 49 ] which showed a significant increase in several Cer species in female ME/CFS patients. Instead, we observed that Hexcer were increased in ME/CFS patients, irrespective of their sex.…”

“…Instead, we observed that Hexcer were increased in ME/CFS patients, irrespective of their sex. Prior studies have shown that HexCer levels are elevated in patients with chronic hepatitis C infection and autoimmune diseases [ 48 , 49 ]. While a role of these sphingolipids remains to be studied in ME/CFS, the above referenced studies do suggest that sphingolipid changes may be associated with autoimmune- and infection-related immune and inflammatory changes observed in ME/CFS patients.…”

Tracking the role of sphingolipids in MS: The dynamic nature of ceramide synthases

“…Date received: 10 January 2022; accepted: 12 January 2022 Dear Editor, In a recent publication in the Multiple Sclerosis Journal, Filippatou et al 1 confirmed that ceramides (Cer) levels are altered in patients with multiple sclerosis (pwMS) and could be associated with both retinal neurodegeneration and physical disability. Prompted by this publication, we would like to raise a few considerations.…”

“…One study that evaluated changes in ceramide synthase mRNA in peripheral blood mononuclear cells (PMBCs) showed changes in the expression of ceramide synthases in people with MS compared to controls. 1 Based on this study and studies documenting alteration in neuroinflammation in experimental autoimmune encephalomyelitis (EAE) in mice lacking these enzymes, 3,4 they propose that measurement of ceramide synthase may be an alternative or superior to measurement of ceramides as biomarkers in MS.…”

The Involvement of Lactosylceramide in Central Nervous System Inflammation Related to Neurodegenerative Disease

“…Each class of gangliosides includes multiple subtypes, and they are involved in a variety of diseases, such as diabetes ( Inokuchi, 2014 ), cancer ( Groux-Degroote et al, 2018 ), and cardiovascular disease. LacCer promotes the accumulation of abnormal proteins ( Srivastava et al, 2019 ), abnormal signaling ( Filippatou et al, 2020 ), and neurotoxicity of gangliosides ( Dhanushkodi et al, 2019 ), which leads to the occurrence and further progression of neurodegenerative diseases.…”