Hexosylceramides as intrathecal markers of worsening disability in multiple sclerosis

Antonio Checa; Mohsen Khademi; Daniel G Sar; Jesper Z Haeggström; Jon O Lundberg; Fredrik Piehl; Tomas Olsson; Craig E Wheelock

doi:10.1177/1352458514561908

Hexosylceramides as intrathecal markers of worsening disability in multiple sclerosis

Mult Scler. 2015 Sep;21(10):1271-9. doi: 10.1177/1352458514561908. Epub 2014 Dec 5.

Authors

Antonio Checa¹, Mohsen Khademi², Daniel G Sar¹, Jesper Z Haeggström¹, Jon O Lundberg³, Fredrik Piehl², Tomas Olsson², Craig E Wheelock⁴

Affiliations

¹ Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
² Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden.
³ Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
⁴ Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden craig.wheelock@ki.se.

PMID: 25480867
DOI: 10.1177/1352458514561908

Abstract

Background: Sphingolipids are important components of neurons and the myelin sheath whose levels are altered in multiple sclerosis (MS).

Objectives: We aimed to determine if cerebrospinal fluid (CSF) sphingolipids can be used as markers of MS disease progression.

Methods: Using liquid chromatography tandem mass spectrometry, we analysed sphingolipids in CSF from 134 individuals. The MS group included 65 patients divided into 41 relapsing-remitting MS (RRMS) and 24 progressive MS (ProgMS). In addition, a group of 13 early MS/clinically isolated syndrome (EarlyMS) and two control groups consisting of 38 individuals with other neurological diseases (OND) and 18 OND with signs of inflammation (iOND) were analysed. A follow-up study included 17 additional RRMS patients sampled at two time points 4.7±1.7 years apart.

Results: Levels of sphingomyelin (SM)- and hexosylceramide (HexCer)-derived sphingolipids increased in the CSF of patients with MS independently of the fatty acid chain length in RRMS (p<0.05). Levels of palmitic acid (16:0)-containing HexCer (HexCer16:0) increased significantly in ProgMS compared with the OND (p<0.001), iOND (p<0.05) and EarlyMS (p<0.01) groups and correlated with Expanded Disability Status Scale in RRMS in both studies (p=0.048; p=0.027).

Conclusion: HexCer16:0 is a promising candidate marker of disease progression in MS, especially in RRMS.

Keywords: Multiple sclerosis; axonal damage; cerebrospinal fluid; demyelination; inflammation; mass spectrometry.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Biomarkers / cerebrospinal fluid*
Ceramides / cerebrospinal fluid*
Disease Progression*
Female
Follow-Up Studies
Humans
Inflammation / cerebrospinal fluid*
Inflammation / diagnosis
Male
Multiple Sclerosis / cerebrospinal fluid*
Multiple Sclerosis / diagnosis*

Substances

Biomarkers
Ceramides