Multiple sclerosis: Identification and clinical evaluation of novel CSF biomarkers.
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.
Ottervald
Jan
J
Neuroimmunology Unit, Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institute at Karolinska University Hospital, Solna, Sweden. jan.ottervald@ki.se
Franzén
Bo
B
Nilsson
Kerstin
K
Andersson
Lars I
LI
Khademi
Mohsen
M
Eriksson
Bodil
B
Kjellström
Sven
S
Marko-Varga
György
G
Végvári
Akos
A
Harris
Robert A
RA
Laurell
Thomas
T
Miliotis
Tasso
T
Matusevicius
Darius
D
Salter
Hugh
H
Ferm
Mats
M
Olsson
Tomas
T
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*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D000069442:Natalizumab