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Mult Scler. 2015 Sep;21(10):1251-61. doi: 10.1177/1352458514561906. Epub 2015 Feb 19.

Chitinase 3-like proteins as diagnostic and prognostic biomarkers of multiple sclerosis.

Author information

1
Institut de Génomique Fonctionnelle, CNRS UMR 5203, INSERM U661, Université Montpellier 1, Université Montpellier 2, France.
2
Service d'Ophtalmologie, Hôpital Gui de Chauliac, CHU de Montpellier, France.
3
Service d'Anatomopathologie, Hôpital Gui de Chauliac, CHU de Montpellier, France.
4
Département d'Information Médicale, CHU de Nîmes, France.
5
Service de Biochimie, Hôpital Gui de Chauliac, CHU de Montpellier, France.
6
Service de Neurologie, Hôpital Gui de Chauliac, CHU de Montpellier, France.
7
Service de Neurologie, Hôpital Carémeau, CHU de Nîmes, France.
8
Service de Neurologie, Hôpital Purpan, CHU de Toulouse, France.
9
Service d'Anatomopathologie, CHU de Nantes, France.
10
INSERM 1064, France.
11
INSERM 1064, France/Service de Neurologie, CHU de Nantes, France.
12
Service de Neurologie, CHU de Grenoble, France.
13
Institut de Génomique Fonctionnelle, CNRS UMR 5203, INSERM U661, Université Montpellier 1, Université Montpellier 2, France/Service de Neurologie, Hôpital Carémeau, CHU de Nîmes, France eric.thouvenot@chu-nimes.fr.

Abstract

BACKGROUND:

Despite sensitivity of MRI to diagnose multiple sclerosis (MS), prognostic biomarkers are still needed for optimized treatment.

OBJECTIVE:

The objective of this paper is to identify cerebrospinal fluid (CSF) diagnostic biomarkers of MS using quantitative proteomics and to analyze their expression at different disease stages.

METHODS:

We conducted differential analysis of the CSF proteome from control and relapsing-remitting MS (RRMS) patients followed by verification by ELISA of candidate biomarkers in CSF and serum in control, clinically isolated syndrome (CIS), RRMS and progressive MS (PMS) patients.

RESULTS:

Twenty-two of the 527 quantified proteins exhibited different abundances in control and RRMS CSF. These include chitinase 3-like protein 1 (CHI3L1) and 2 (CHI3L2), which showed a strong expression in brain of MS patients, especially in astrocytes and microglial cells from white matter plaques. CSF and serum CHI3L1 levels increased with the disease stage and CIS patients with high CSF (>189 ng/ml) and serum (>33 ng/ml) CHI3L1 converted more rapidly to RRMS (log rank test, p < 0.05 and p < 0.001, respectively). In contrast, CSF CHI3L2 levels were lower in PMS than in RRMS patients. Accordingly, CSF CHI3L1/CHI3L2 ratio accurately discriminated PMS from RRMS.

CONCLUSIONS:

CSF CHI3L1 and CHI3L2 and serum CHI3L1 might help to define MS disease stage and have a prognostic value in CIS.

KEYWORDS:

Multiple sclerosis; biomarkers; cerebrospinal fluid; diagnosis; prognosis; proteomics

PMID:
25698171
DOI:
10.1177/1352458514561906
[Indexed for MEDLINE]
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