Distinctive sphingolipid patterns in chronic multiple sclerosis lesions.

Multiple sclerosis (MS) is a CNS disease characterized by immune-mediated demyelination and progressive axonal loss. MS-related CNS damage and its clinical course have two main phases: active and inactive/progressive. Reliable biomarkers are being sought to allow identification of MS pathomechanisms and prediction of its course. The purpose of this study was to identify sphingolipid (SL) species as candidate biomarkers of inflammatory and neurodegenerative processes underlying MS pathology. We performed sphingolipidomic analysis by high-performance liquid chromatography-tandem mass spectrometry to determine the lipid profiles in post mortem specimens from the normal appearing white matter (NAWM) of normal CNS (nCNS), from subjects with chronic MS (active and inactive lesions) as well as from patients with other neurological diseases. Distinctive SL modification patterns occurred in specimens from MS patients with chronic inactive plaques with respect to NAWM from nCNS and active MS lesions. Chronic inactive MS lesions were characterized by decreased level of dihydroceramide (dhCer), ceramide, and sphingomyelin subspecies whereas level of hexosylceramide and ceramide-1-phosphate (C1P) subspecies was significantly increased in comparison to NAWM of nCNS as well as active MS plaques. In contrast, active MS lesions were characterized by a significant increase of major dhCer subspecies in comparison to NAWM of nCNS. These results suggest the existence of different SL metabolic pathways in the active versus inactive phase within progressive stage of MS. Moreover, they suggest that C1P could be a new biomarker of inactive MS progressive phase, and its detection may help to develop future prognostic and therapeutic strategies for the disease.