title: Multiple sclerosis: Identification and clinical evaluation of novel CSF biomarkers.
abstract: Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that results in damage to myelin sheaths and axons in the central nervous system and which preferentially affects young adults. We performed a proteomics-based biomarker discovery study in which cerebrospinal fluid (CSF) from MS and control individuals was analyzed (n=112). Ten candidate biomarkers were selected for evaluation by quantitative immunoassay using an independent cohort of MS and control subjects (n=209). In relapsing-remitting MS (RRMS) patients there were significant increases in the CSF levels of alpha-1 antichymotrypsin (A1AC), alpha-1 macroglobulin (A2MG) and fibulin 1 as compared to control subjects. In secondary progressive MS (SPMS) four additional proteins (contactin 1, fetuin A, vitamin D binding protein and angiotensinogen (ANGT)) were increased as compared to control subjects. In particular, ANGT was increased 3-fold in SPMS, indicating a potential as biomarker of disease progression in MS. In PPMS, A1AC and A2MG exhibit significantly higher CSF levels than controls, with a trend of increase for ANGT. Classification models based on the biomarker panel could identify 70% of the RRMS and 80% of the SPMS patients correctly. Further evaluation was conducted in a pilot study of CSF from RRMS patients (n=36), before and after treatment with natalizumab.
authors.affiliation: Neuroimmunology Unit, Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institute at Karolinska University Hospital, Solna, Sweden. jan.ottervald@ki.se
authors.forename: Jan
authors.initials: J
authors.lastname: Ottervald
authors.forename: Bo
authors.initials: B
authors.lastname: Franzén
authors.forename: Kerstin
authors.initials: K
authors.lastname: Nilsson
authors.forename: Lars I
authors.initials: LI
authors.lastname: Andersson
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khademi
authors.forename: Bodil
authors.initials: B
authors.lastname: Eriksson
authors.forename: Sven
authors.initials: S
authors.lastname: Kjellström
authors.forename: György
authors.initials: G
authors.lastname: Marko-Varga
authors.forename: Akos
authors.initials: A
authors.lastname: Végvári
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harris
authors.forename: Thomas
authors.initials: T
authors.lastname: Laurell
authors.forename: Tasso
authors.initials: T
authors.lastname: Miliotis
authors.forename: Darius
authors.initials: D
authors.lastname: Matusevicius
authors.forename: Hugh
authors.initials: H
authors.lastname: Salter
authors.forename: Mats
authors.initials: M
authors.lastname: Ferm
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D020528:Multiple Sclerosis, Chronic Progressive / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D000069442:Natalizumab; D010865:Pilot Projects; D040901:Proteomics / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D000069442:Natalizumab