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

Multiple Sclerosis Journal - Tập 21 Số 10 - Trang 1251-1261 - 2015
Geoffrey Hinsinger1, Nicoletta Galeotti1, Nicolas Nabholz2, Serge Urbach1, Valérie Rigau3, Christophe Dematteï4, Sylvain Lehmann5, William Camu6, Pierre Labauge6, Giovanni Castelnovo7, Pierre Labauge8, Marc G. Denis9, Marion Salou10, Olivier Casez11, Joël Bockaert1, Philippe Marin1, Éric Thouvenot12
1Institut de Génomique Fonctionnelle, CNRS UMR 5203, INSERM U661, Université Montpellier 1, Université Montpellier 2, France
2Service d'Ophtalmologie [Montpellier] (80 Avenue Augustin Fliche, 34295 Montpellier cedex 5 - France)
3Service d’Anatomopathologie, Hôpital Gui de Chauliac, CHU de Montpellier, France
4Département d’Information Médicale, CHU de Nîmes, France
5Service de Biochimie, Hôpital Gui de Chauliac, CHU de Montpellier, France
6Service de Neurologie, Hôpital Gui de Chauliac, CHU de Montpellier, France
7Service de Neurologie, Hôpital Carémeau, CHU de Nîmes, France
8Service de Neurologie, Hôpital Purpan, CHU de Toulouse, France
9CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (1 Place Alexis-Ricordeau, 44000 Nantes - France)
10INSERM 1064, France
11Service de Neurologie, CHU de Grenoble, France
12Institut de Génomique Fonctionnelle, CNRS UMR 5203, INSERM U661, Université Montpellier 1, Université Montpellier 2, France/Service de Neurologie, Hôpital Carémeau, CHU de Nîmes, France

Tóm tắt

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.

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Tài liệu tham khảo

10.1002/ana.22366

10.1016/S1474-4422(06)70353-2

10.1016/j.jns.2011.03.026

10.1191/135248506ms1263oa

10.1212/WNL.0b013e31821432ff

10.1002/prca.201200104

10.1111/j.1468-1331.2008.02239.x

10.1191/1352458504ms1023oa

Kroksveen AC, Acta Neurol Scand Suppl, 2012, 90

10.1177/1352458507076406

10.1021/pr0504788

10.1016/j.jprot.2010.01.004

10.1002/pmic.200700446

10.1021/pr8010155

10.1371/journal.pone.0012442

10.1016/j.neulet.2009.01.057

10.1093/brain/awq035

10.1212/WNL.0b013e318275979d

R Development Core Team, 2011, R: A language and environment for statistical computing

10.1002/ana.20703

10.1002/1531-8249(200006)47:6<707::AID-ANA3>3.0.CO;2-Q

10.1016/j.rmed.2004.09.016

10.1093/rheumatology/38.7.618

10.1007/s00384-002-0446-z

10.1146/annurev-physiol-012110-142250

10.1080/03009740510018598

10.1111/j.1750-3639.2011.00550.x

10.1186/1742-2094-7-34

10.2353/ajpath.2008.080045

10.1074/jbc.M211980200

10.1021/pr3012107

10.1016/j.cellsig.2013.03.016

10.1177/1352458511433063

10.1016/S0009-8981(01)00573-3

Tsuruha J, 2002, J Rheumatol, 29, 1459

10.1136/ard.60.1.49

10.1074/jbc.271.32.19415

10.7150/ijbs.8.39

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Multiple Sclerosis Journal

Tập 21 Số 10

1251-1261

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