title: Effects of natalizumab treatment on the cerebrospinal fluid proteome of multiple sclerosis patients.
abstract: Natalizumab is a very effective, relatively new drug for the treatment of relapsing remitting multiple sclerosis. Inflammatory and neurodegenerative processes in the central nervous system are presumed to cause adverse effects during the course of this disease. To monitor the effects of natalizumab treatment on the cerebrospinal fluid (CSF) proteome of patients, CSF samples were taken from patients before commencing treatment as well as after 1 year of treatment. Profiling proteomics experiments using electrospray Orbitrap mass spectrometry and pair wise comparison of patients before and after 1 year of natalizumab treatment revealed a number of candidate biomarkers that were significantly differentially abundant between the before and after treatment groups. Three proteins were subsequently validated using selected reaction monitoring (SRM) in a new, independent sample set. All three proteins, Ig mu chain C region and haptoglobin, both known inflammation-related proteins, as well as Chitinase-3-like protein 1, were confirmed by SRM to be significantly lower abundant in CSF of multiple sclerosis patients after 1 year of natalizumab treatment. The findings for Chitinase-3-like protein 1, a presumed biomarker for more rapid progression from a first clinically isolated syndrome to clinically definite multiple sclerosis, was further confirmed by ELISA measurements.
authors: Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Marcel P
authors: MP
authors: Stoop
authors: Vaibhav
authors: V
authors: Singh
authors: Christoph
authors: C
authors: Stingl
authors: Roland
authors: R
authors: Martin
authors: Mohsen
authors: M
authors: Khademi
authors: Tomas
authors: T
authors: Olsson
authors: Rogier Q
authors: RQ
authors: Hintzen
authors: Theo M
authors: TM
authors: Luider
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis* / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D000069442:Natalizumab; D020543:Proteome; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins; D000069442:Natalizumab; D020543:Proteome