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Multiple sclerosis-related proteins identified in cerebrospinal fluid by advanced mass spectrometry

Authors

  • Marcel P. Stoop,

    1. Laboratories of Neuro-Oncology / Clinical and Cancer Proteomics, Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands
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  • Lennard J. Dekker,

    1. Laboratories of Neuro-Oncology / Clinical and Cancer Proteomics, Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands
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  • Mark K. Titulaer,

    1. Laboratories of Neuro-Oncology / Clinical and Cancer Proteomics, Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands
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  • Peter C. Burgers,

    1. Laboratories of Neuro-Oncology / Clinical and Cancer Proteomics, Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands
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  • Peter A. E. Sillevis Smitt,

    1. Laboratories of Neuro-Oncology / Clinical and Cancer Proteomics, Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands
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  • Theo M. Luider Dr.,

    Corresponding author
    1. Laboratories of Neuro-Oncology / Clinical and Cancer Proteomics, Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands
    • Laboratories of Neuro-Oncology/Clinical and Cancer Proteomics, Department of Neurology, Erasmus University Medical Centre, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands Fax: +31-10-408-8365
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  • Rogier Q. Hintzen

    1. Laboratories of Neuro-Oncology / Clinical and Cancer Proteomics, Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands
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Abstract

A total of 164 cerebrospinal fluid (CSF) samples taken from neurological patients were classed into four groups according to the clinical diagnosis: multiple sclerosis (MScl, n = 44), clinically isolated syndrome of demyelination (CIS, n = 40), other inflammatory neurological disease (OIND, n = 26) and other neurological disease (OND, n = 54). After tryptic digestion, the samples were measured by MALDI-TOF MS. Spectra were analyzed using the R-project software package, in which a peak detection algorithm was developed. Subsequently, the peak lists were compared based on ranked data (non-parametric). Significant differences were observed in the comparisons of MScl vs. OND and CIS vs. OND. The comparisons of MScl vs. OIND, and CIS vs. OIND showed fewer significant differences. No significant differences were found in comparisons MScl vs. CIS and OIND vs. OND. MScl and CIS had strikingly similar profiles, probably a reflection of common pathological mechanisms. Three differentially expressed proteins in the comparison of MScl vs. OND were identified: chromogranin A, a potential marker for neurodegeneration; and two important factors in complement-mediated inflammatory reaction, clusterin and complement C3. CSF chromogranin A levels were confirmed to be significantly elevated in the MScl group using an ELISA.

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