title: Chitinase 3-like proteins as diagnostic and prognostic biomarkers of multiple sclerosis.
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.
authors.affiliation: Institut de Génomique Fonctionnelle, CNRS UMR 5203, INSERM U661, Université Montpellier 1, Université Montpellier 2, France.
authors.forename: G
authors.initials: G
authors.lastname: Hinsinger
authors.affiliation: Institut de Génomique Fonctionnelle, CNRS UMR 5203, INSERM U661, Université Montpellier 1, Université Montpellier 2, France.
authors.forename: N
authors.initials: N
authors.lastname: Galéotti
authors.affiliation: Service d'Ophtalmologie, Hôpital Gui de Chauliac, CHU de Montpellier, France.
authors.forename: N
authors.initials: N
authors.lastname: Nabholz
authors.affiliation: Institut de Génomique Fonctionnelle, CNRS UMR 5203, INSERM U661, Université Montpellier 1, Université Montpellier 2, France.
authors.forename: S
authors.initials: S
authors.lastname: Urbach
authors.affiliation: Service d'Anatomopathologie, Hôpital Gui de Chauliac, CHU de Montpellier, France.
authors.forename: V
authors.initials: V
authors.lastname: Rigau
authors.affiliation: Département d'Information Médicale, CHU de Nîmes, France.
authors.forename: C
authors.initials: C
authors.lastname: Demattei
authors.affiliation: Service de Biochimie, Hôpital Gui de Chauliac, CHU de Montpellier, France.
authors.forename: S
authors.initials: S
authors.lastname: Lehmann
authors.affiliation: Service de Neurologie, Hôpital Gui de Chauliac, CHU de Montpellier, France.
authors.forename: W
authors.initials: W
authors.lastname: Camu
authors.affiliation: Service de Neurologie, Hôpital Gui de Chauliac, CHU de Montpellier, France.
authors.forename: P
authors.initials: P
authors.lastname: Labauge
authors.affiliation: Service de Neurologie, Hôpital Carémeau, CHU de Nîmes, France.
authors.forename: G
authors.initials: G
authors.lastname: Castelnovo
authors.affiliation: Service de Neurologie, Hôpital Purpan, CHU de Toulouse, France.
authors.forename: D
authors.initials: D
authors.lastname: Brassat
authors.affiliation: Service d'Anatomopathologie, CHU de Nantes, France.
authors.forename: D
authors.initials: D
authors.lastname: Loussouarn
authors.affiliation: INSERM 1064, France.
authors.forename: M
authors.initials: M
authors.lastname: Salou
authors.affiliation: INSERM 1064, France/Service de Neurologie, CHU de Nantes, France.
authors.forename: D
authors.initials: D
authors.lastname: Laplaud
authors.affiliation: Service de Neurologie, CHU de Grenoble, France.
authors.forename: O
authors.initials: O
authors.lastname: Casez
authors.affiliation: Institut de Génomique Fonctionnelle, CNRS UMR 5203, INSERM U661, Université Montpellier 1, Université Montpellier 2, France.
authors.forename: J
authors.initials: J
authors.lastname: Bockaert
authors.affiliation: Institut de Génomique Fonctionnelle, CNRS UMR 5203, INSERM U661, Université Montpellier 1, Université Montpellier 2, France.
authors.forename: P
authors.initials: P
authors.lastname: Marin
authors.affiliation: 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.
authors.forename: E
authors.initials: E
authors.lastname: Thouvenot
mesh_terms: D054392:Adipokines / Q000097:blood* / Q000134:cerebrospinal fluid*; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism; D000071451:Chitinase-3-Like Protein 1; D002688:Chitinases / Q000097:blood / Q000134:cerebrospinal fluid*; D018450:Disease Progression; D005260:Female; D006801:Humans; D037102:Lectins / Q000097:blood* / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D040901:Proteomics
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; C571841:CHI3L2 protein, human; D002688:Chitinases
keywords: Multiple sclerosis; biomarkers; cerebrospinal fluid; diagnosis; prognosis; proteomics