Cerebrospinal fluid concentrations of peptides derived from chromogranin B and secretogranin II are decreased in multiple sclerosis.
Novel biomarkers for multiple sclerosis (MS) could improve diagnosis and provide clues to pathogenesis. In this study surface-enhanced laser desorption/ionization time-of-flight mass spectrometry was used to analyze protein expression in CSF from 46 MS patients, 46 healthy siblings to the patients, and 50 unrelated healthy controls. Twenty-four proteins in the mass range 2-10 kDa were expressed at significantly different levels (p < 0.01) in a robust manner when comparing the three groups. Identities of three proteins were determined using biochemical purification followed by tandem mass spectrometric analysis. Immunoprecipitation experiments confirmed the identities for two peptides derived from chromogranin B (m/z 6252) and from secretogranin II (m/z 3679). These peptides were all decreased in MS when compared with siblings or controls. Radioimmunoassays specific for each peptide confirmed these differences. The lowered concentrations did not correlate to the axonal damage marker neurofilament light protein and may thus reflect functional changes rather than neurodegeneration. Further studies will investigate the involvement of these peptides in MS pathogenesis.
Mattsson
Niklas
N
Department of Neurochemistry and Psychiatry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, Mölndal, Sweden. niklas.mattsson@neuro.gu.se
Rüetschi
Ulla
U
Podust
Vladimir N
VN
Stridsberg
Mats
M
Li
Susann
S
Andersen
Oluf
O
Haghighi
Sara
S
Blennow
Kaj
K
Zetterberg
Henrik
H
D000328:Adult; D053378:Chromogranin B / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid*; D009479:Neuropeptides / Q000134:cerebrospinal fluid*; D010449:Peptide Mapping / Q000379:methods; D011863:Radioimmunoassay / Q000379:methods; D053381:Secretogranin II / Q000134:cerebrospinal fluid*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D018709:Statistics, Nonparametric
D053378:Chromogranin B; D009479:Neuropeptides; D053381:Secretogranin II