title: CSF inflammation and axonal damage are increased and correlate in progressive multiple sclerosis.
abstract: BACKGROUND
  The mechanism underlying disease progression in progressive multiple sclerosis (MS) is uncertain. Pathological studies found widespread inflammation in progressive MS brains correlating with disease progression and axonal damage.
  
  
  OBJECTIVE
  To study cerebrospinal fluid (CSF) biomarkers and clarify whether inflammation and axonal damage are associated in progressive MS.
  
  
  METHODS
  Using enzyme-linked immunosorbent assay (ELISA), we analysed CSF from 40 secondary progressive (SPMS), 21 primary progressive (PPMS), and 36 relapsing-remitting (RRMS) and 20 non-inflammatory neurological disease (NIND) patients. Twenty-two of the SPMS patients participated in an MBP8298 peptide clinical trial and had CSF follow-up after one year.
  
  
  RESULTS
  Compared to NIND patients, inflammatory biomarkers osteopontin and matrix metalloproteinase-9 (MMP9) were increased in all MS patients while CXCL13 was increased in RRMS and SPMS patients. Biomarkers of axonal damage (NFL) and demyelination (MBP) were increased in all MS patients. In progressive MS patients CSF levels of osteopontin and CXCL13 correlated with NFL while osteopontin and MMP9 correlated with MBP. MBP8298 treatment did not affect the levels of the biomarkers after one year of treatment. All biomarkers were continuously increased after one year of follow-up except MBP, which decreased.
  
  
  CONCLUSIONS
  CSF biomarkers of inflammation, axonal damage and demyelination are continuously increased in progressive MS patients and correlate. These findings parallel pathology studies, emphasise a relationship between inflammation, axonal damage and demyelination and support the use of CSF biomarkers in progressive MS clinical trials.
authors.affiliation: University of Copenhagen and Department of Neurology, Copenhagen University Hospital Rigshospitalet, Denmark. jeppe.romme.christensen@rh.regionh.dk
authors.forename: Jeppe
authors.initials: J
authors.lastname: Romme Christensen
authors.forename: Lars
authors.initials: L
authors.lastname: Börnsen
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khademi
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Poul Erik
authors.initials: PE
authors.lastname: Jensen
authors.forename: Per Soelberg
authors.initials: PS
authors.lastname: Sørensen
authors.forename: Finn
authors.initials: F
authors.lastname: Sellebjerg
mesh_terms: D000328:Adult; D001369:Axons / Q000473:pathology*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000134:cerebrospinal fluid* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000134:cerebrospinal fluid* / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid / Q000473:pathology
chemical_list: D015415:Biomarkers