Antonio Checa1, Mohsen Khademi2, Daniel G Sar1, Jesper Z Haeggström1, Jon O Lundberg3, Fredrik Piehl2, Tomas Olsson2, Craig E Wheelock4. 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.
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.
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.
Authors: Antonio Checa; Ning Xu; Daniel G Sar; Jesper Z Haeggström; Mona Ståhle; Craig E Wheelock Journal: Sci Rep Date: 2015-07-15 Impact factor: 4.379
Authors: Florian M Ottenlinger; Christoph A Mayer; Nerea Ferreirós; Yannick Schreiber; Anja Schwiebs; Katrin G Schmidt; Hanns Ackermann; Josef M Pfeilschifter; Heinfried H Radeke Journal: Front Pharmacol Date: 2016-11-03 Impact factor: 5.810
Authors: Marcus O D Sjödin; Antonio Checa; Mingxing Yang; Sven-Erik Dahlén; Åsa M Wheelock; Anders Eklund; Johan Grunewald; Craig E Wheelock Journal: Respir Res Date: 2018-12-03
Authors: Lachlan Porter; Alireza Shoushtarizadeh; George A Jelinek; Chelsea R Brown; Chai K Lim; Alysha M de Livera; Kelly R Jacobs; Tracey J Weiland Journal: Front Mol Biosci Date: 2020-12-14
Authors: Antonio Checa; Tina Holm; Marcus O D Sjödin; Stacey N Reinke; Johan Alm; Annika Scheynius; Craig E Wheelock Journal: Sci Rep Date: 2015-11-02 Impact factor: 4.379