| Cerebrospinal fluid chitinase 3-like 1 levels are associated with conversion to multiple sclerosis. | |
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MedLine Citation:
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PMID: 20237129 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In most patients with multiple sclerosis, the disease initiates with a first attack or clinically isolated syndrome. At this phase, magnetic resonance imaging is an important predictor of conversion to multiple sclerosis. With the exception of oligoclonal bands, the role of other biomarkers in patients with clinically isolated syndrome is controversial. In the present study, we aimed to identify proteins associated with conversion to multiple sclerosis in patients with clinically isolated syndrome. We applied a mass spectrometry-based proteomic approach (isobaric labelling) to previously collected pooled cerebrospinal fluid samples from patients with clinically isolated syndrome, who subsequently converted to clinically definite multiple sclerosis (n=30) and patients who remained as having clinically isolated syndrome (n=30). Next, three of the most represented differentially expressed proteins, i.e. ceruloplasmin, vitamin D-binding protein and chitinase 3-like 1 were selected for validation in individual cerebrospinal fluid samples by enzyme-linked immunosorbent assay. Only chitinase 3-like 1 was validated and cerebrospinal fluid levels were increased in patients who converted to clinically definite multiple sclerosis compared with patients who continued as clinically isolated syndrome (P=0.00002) and controls (P=0.012). High cerebrospinal fluid levels of chitinase 3-like 1 significantly correlated with the number of gadolinium enhancing lesions and the number of T2 lesions observed in brain magnetic resonance imaging scans performed at baseline, and were associated with disability progression during follow-up and shorter time to clinically definite multiple sclerosis (log-rank P-value=0.003). Cerebrospinal fluid chitinase 3-like 1 levels were also measured in a second validation clinically isolated syndrome cohort and found to be increased in patients who converted to multiple sclerosis compared with patients who remained as having clinically isolated syndrome (P=0.018). Our results indicate that patients who will convert to clinically definite multiple sclerosis could be distinguished from those patients who will remain as clinically isolated syndrome by proteomic analysis of cerebrospinal fluid samples. Although protein levels are also increased in other disorders characterized by chronic inflammation, chitinase 3-like 1 may serve as a prognostic biomarker for conversion to multiple sclerosis and development of disability which may help to improve the understanding of the aetiopathogenesis in the early stages of multiple sclerosis. |
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Authors:
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Manuel Comabella; Marta Fern?ndez; Roland Martin; Stephanie Rivera-Vallv?; Eva Borr?s; Cristina Chiva; Eva Juli?; Alex Rovira; Ester Cant?; Jose Carlos Alvarez-Cerme?o; Luisa Mar?a Villar; Mar Tintor?; Xavier Montalban |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-17 |
Journal Detail:
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Title: Brain : a journal of neurology Volume: 133 ISSN: 1460-2156 ISO Abbreviation: Brain Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-08 Completed Date: 2010-04-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372537 Medline TA: Brain Country: England |
Other Details:
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Languages: eng Pagination: 1082-93 Citation Subset: AIM; IM |
Affiliation:
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Centre d'Esclerosi M?ltiple de Catalunya, CEM-Cat, Unitat de Neuroimmunologia Cl?nica, Hospital Universitari Vall d'Hebron (HUVH), Barcelona 08035, Spain. mcomabel@ir.vhebron.net |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Biological Markers / cerebrospinal fluid Cohort Studies Disease Progression Female Follow-Up Studies Glycoproteins / cerebrospinal fluid*, genetics Humans Lectins / cerebrospinal fluid*, genetics Male Middle Aged Multiple Sclerosis / cerebrospinal fluid, diagnosis*, enzymology* Predictive Value of Tests Proteomics / methods Syndrome Young Adult |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/CHI3L1 protein, human; 0/Glycoproteins; 0/Lectins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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