Sulfatide isoform pattern in cerebrospinal fluid discriminates progressive MS from relapsing‐remitting MS

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Several biomarkers including proteins and lipids have been reported in MS cerebrospinal fluid (CSF), reflecting different aspects of the pathophysiology particularly of relapsing-remitting MS (RRMS). Sulfatide, abundant in the myelin sheath and a proposed target for autoimmune attack in MS, has been reported altered in MS CSF. Here, we investigated the potential of CSF sulfatide and its isoforms as biomarkers in MS. A highly sensitive and quantitative mass spectrometry method was employed to determine levels of sulfatide isoforms in CSF from RRMS and progressive MS (PMS) patients, and healthy donors (HD). We demonstrate that levels of total CSF sulfatide and C24:1, C26:1, and C26:1-OH isoforms were significantly increased in PMS compared with RRMS patients and HD, while C23:0-OH was significantly decreased in CSF from PMS patients compared to the other two groups. Multivariate discriminant analysis showed that CSF sulfatide isoform pattern in PMS patients was distinct and non-overlapping with that of RRMS patients and HD. Sulfatide levels did not correlate with tested biomarkers or clinical parameters. The results suggest that CSF sulfatide isoform levels may be used to discriminate the phenotype of MS and might play a role in the progression of the disease.

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“…Since vitamin K stimulates sulfatide biosynthesis in the brain, the vitamin K antagonist warfarin impairs brain sulfatide [ 41 ]. Sulfatide, on the other hand, may have a role in the pathogenesis of autoimmunity by acting as a possible ligand for L and P-selectin and up-regulating the expression of chemokine co-receptors (CXCR4) on neutrophils [ 42 ]. In an experimental investigation, sulfatide stimulates the replication of influenza A virus and hepatitis C virus (HCV) [ 43 , 44 ].…”

Next-Generation Neuroimmunology: New Technologies to Understand Central Nervous System Autoimmunity

“…In MS, metabolomics showed discrete metabolite profiles of CSF [92]. Other studies found the CSF metabolome to distinguish MS and NOSD [93], as well as between secondary progressive MS and relapsingremitting MS [94]. One can envision that the differential diagnosis of nervous system autoimmune diseases might be supported by a panel of proteins or metabolites in the future.…”

Importance of Lipids for Nervous System Integrity: Cooperation between Gangliosides and Sulfatides in Myelin Stability

“…Through effects on protein localization, glycosphingolipids might play a role in the dysmyelination or demyelination processes observed in several pathologies. Indeed, various demyelinating diseases, including multiple sclerosis (MS), are associated with alteration of gangliosides and/or sulfatides (Novakova et al, 2018). Differences in the level and nature of sulfatides have been observed, especially in cerebrospinal fluid of patients with progressive MS compared with healthy do-nors or patients with relapsing-remitting MS (Novakova et al, 2018).…”

“…Indeed, various demyelinating diseases, including multiple sclerosis (MS), are associated with alteration of gangliosides and/or sulfatides (Novakova et al, 2018). Differences in the level and nature of sulfatides have been observed, especially in cerebrospinal fluid of patients with progressive MS compared with healthy do-nors or patients with relapsing-remitting MS (Novakova et al, 2018). Surprisingly, in addition to reporting a possible reduction of sulfatide in the normal-appearing white matter of MS patients, Marbois et al (2000) showed a significant alteration in the sulfatide species present in MS.…”