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In search of cerebrospinal fluid biomarkers of fatigue in multiple sclerosis: A proteomics study
Author(s) -
Valko Philipp O.,
Roschitzki Bernd,
Faigle Wolfgang,
Grossmann Jonas,
Panse Christian,
Biro Peter,
Dambach Micha,
Spahn Donat R.,
Weller Michael,
Martin Roland,
Baumann Christian R.
Publication year - 2019
Publication title -
journal of sleep research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.297
H-Index - 117
eISSN - 1365-2869
pISSN - 0962-1105
DOI - 10.1111/jsr.12721
Subject(s) - multiple sclerosis , cerebrospinal fluid , proteomics , proteome , shotgun proteomics , quantitative proteomics , medicine , pathology , bioinformatics , biology , immunology , biochemistry , gene
Summary Fatigue in multiple sclerosis is a very common and cumbersome symptom, but its aetiology is poorly understood. Proteomics is increasingly implemented in multiple sclerosis research, but has not yet been used to study the neurobiological basis of fatigue in multiple sclerosis. To identify potential cerebrospinal fluid biomarkers of fatigue in multiple sclerosis, we collected cerebrospinal fluid of 20 patients with multiple sclerosis with fatigue (MS+), 20 patients with multiple sclerosis without fatigue (MS−), and 20 control subjects without multiple sclerosis and without fatigue (HC). We used a shotgun proteomics approach and label‐free quantitative proteomics to analyse the protein content in cerebrospinal fluid. Selected proteins with differential abundance were further validated by immunoblotting. Out of 591 detected cerebrospinal fluid proteins, the abundance of nine proteins differed between the three groups, and seven additional proteins differed between MS+ and MS− patients. Using immunoblot or slot‐blot techniques, we confirmed decreased levels of protein kinase C‐binding protein NELL2, neural cell adhesion molecule L1‐like protein, and reelin in MS+ patients. In conclusion, cerebrospinal fluid proteomics may provide insight into the neurobiological basis of fatigue in multiple sclerosis. The proteins identified to be decreased in MS+ are involved in synaptic plasticity and energy homeostasis, and thus appear as plausible biomarkers of this common symptom.