Acta Neurologica Belgica

, Volume 119, Issue 1, pp 101–111 | Cite as

Identification of candidate biomarkers in converting and non-converting clinically isolated syndrome by proteomics analysis of cerebrospinal fluid

  • O. Timirci-Kahraman
  • Z. Karaaslan
  • E. Tuzun
  • M. Kurtuncu
  • A. T. Baykal
  • T. Gunduz
  • M. B. Tuzuner
  • E. Akgun
  • B. Gurel
  • M. Eraksoy
  • Cem Ismail KucukaliEmail author
Original Article


Multiple sclerosis (MS) often starts in the form of clinically isolated syndrome (CIS) and only some of the CIS patients progress to relapsing-remitting MS (RRMS). Biomarkers to predict conversion from CIS to MS are thus greatly needed for making correct treatment decisions. To identify a predictive cerebrospinal fluid (CSF) protein, we analyzed the first-attack CSF samples of CIS patients who converted (CIS–MS) (n = 23) and did not convert (CIS–CIS) (n = 19) to RRMS in a follow-up period of 5 years using proteomics analysis by liquid chromatography tandem-mass spectrometry (LC–MS/MS) and verified by ELISA. Label-free differential proteomics analysis of CSF ensured that 637 proteins were identified and 132 of these proteins were found to be statistically significant. Further investigation with the ingenuity pathway analysis (IPA) software led to identification of three pathway networks mostly comprised proteins involved in inflammatory response, cellular growth and tissue proliferation. CSF levels of four of the most differentially expressed proteins belonging to the cellular proliferation network function, chitinase-3-like protein 1 (CHI3L1), tumor necrosis factor receptor superfamily member 21 (TNFRSF21), homeobox protein Hox-B3 (HOXB3) and iduronate 2-sulfatase (IDS), were measured by ELISA. CSF levels of HOXB3 were significantly increased in CIS–MS patients. Our results indicate that cell and tissue proliferation functions are dysregulated in MS as early as the first clinical episode. HOXB3 has emerged as a potential novel biomarker which might be used for prediction of CIS–MS conversion.


Multiple sclerosis Clinically isolated syndrome Homeobox protein Hox-B3 Mass spectrometry Proteomics 



This project was supported by BAP Project of Istanbul University (Project no: TYD-2017-24256).

Compliance with ethical standards

Conflict of interest

The authors declare no financial or other conflicts of interest.

Ethical standards

All study enrolment followed the recommendations of the Declaration of Helsinki and the study approved by the Medical Ethics Committee of Istanbul Medical Faculty.

Informed consent

Informed consents were obtained from all patients or their legal guardians and controls, following provision of detailed information on the study examinations and tests.

Supplementary material

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Supplementary material 1 (DOC 27 KB)
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Supplementary material 2 (XLS 2049 KB)
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Supplementary material 3 (XLS 134 KB)
13760_2018_954_MOESM4_ESM.xlsx (12 kb)
Supplementary material 4 (XLSX 11 KB)


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Copyright information

© Belgian Neurological Society 2018

Authors and Affiliations

  • O. Timirci-Kahraman
    • 1
  • Z. Karaaslan
    • 2
  • E. Tuzun
    • 3
  • M. Kurtuncu
    • 2
  • A. T. Baykal
    • 4
  • T. Gunduz
    • 2
  • M. B. Tuzuner
    • 5
  • E. Akgun
    • 4
  • B. Gurel
    • 4
  • M. Eraksoy
    • 2
  • Cem Ismail Kucukali
    • 3
    Email author
  1. 1.Department of Molecular Medicine, Aziz Sancar Institute of Experimental MedicineIstanbul UniversityIstanbulTurkey
  2. 2.Department of Neurology, Faculty of MedicineIstanbul UniversityIstanbulTurkey
  3. 3.Department of Neuroscience, Aziz Sancar Institute of Experimental MedicineIstanbul UniversityIstanbulTurkey
  4. 4.Department of Medical Biochemistry, Faculty of MedicineAcibadem Mehmet Ali Aydinlar UniversityIstanbulTurkey
  5. 5.Acibadem Labmed R&D LaboratoryIstanbulTurkey

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