Serum ceramide levels are altered in multiple sclerosis.

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 ( = 251) and HCs ( = 68). For a subset of PwMS, baseline and 5-year Expanded Disability Status Scale (EDSS) assessments ( = 185), or baseline and serial spectral-domain OCT ( = 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,  = 0.01; -0.158 ± 0.053,  = 0.003, respectively) and peripapillary retinal nerve fiber layer thinning (-0.305 ± 0.107,  = 0.004; -0.358 ± 0.106,  = 0.001, respectively).

CONCLUSION

Ceramide levels are altered in PwMS and may be associated with retinal neurodegeneration and physical disability.