Cerebrospinal fluid chitinase 3-like 1 levels are associated with conversion to multiple sclerosis
Manuel Comabella,M. Fernández,Roland Martin,Stephanie Rivera-Vallvé,Eva Borràs,Cristina Chiva,Eva Julià,Alex Rovira,Ester Cantó,José C. Álvarez-Cermeño,Luisa M. Villar,Mar Tintoré,Xavier Montalban +12 more
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TLDR
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.Abstract:
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.read more
Citations
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YKL-40: A Novel Prognostic Fluid Biomarker for Preclinical Alzheimer's Disease
Rebecca Craig-Schapiro,Richard J. Perrin,Catherine M. Roe,Chengjie Xiong,Deborah Carter,Nigel J. Cairns,Mark A. Mintun,Elaine R. Peskind,Elaine R. Peskind,Ge Li,Douglas Galasko,Christopher M. Clark,Joseph F. Quinn,Gina D'Angelo,James P. Malone,R. Reid Townsend,John C. Morris,Anne M. Fagan,David M. Holtzman +18 more
TL;DR: These data demonstrate that YKL-40, a putative indicator of neuroinflammation, is elevated in AD and, together with Aβ42, has potential prognostic utility as a biomarker for preclinical AD.
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Neurofilaments as biomarkers in multiple sclerosis
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The utility of cerebrospinal fluid analysis in patients with multiple sclerosis
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TL;DR: CSF findings that shed light on the differential diagnosis of MS are summarized, the potential of novel biomarkers for this disease that could advance understanding of its pathophysiology are highlighted.
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References
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Journal ArticleDOI
New diagnostic criteria for multiple sclerosis: guidelines for research protocols.
Charles M. Poser,Donald W. Paty,Labe C. Scheinberg,W I McDonald,F A Davis,George C. Ebers,Kenneth P. Johnson,William A. Sibley,Donald H. Silberberg,Wallace W. Tourtellotte +9 more
TL;DR: Today there is a need for more exact criteria than existed earlier in order to conduct therapeutic trials in multicenter programs, to compare epidemiological surveys, to evaluate new diagnostic procedures, and to estimate the activity of the disease process in MS.
Journal ArticleDOI
Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis
W. Ian McDonald,A Compston,Gilles Edan,Donald E. Goodkin,Hans-Peter Hartung,Fred D. Lublin,Henry F. McFarland,Donald W. Paty,Chris H. Polman,Stephen C. Reingold,Magnhild Sandberg-Wollheim,William A. Sibley,Alan J. Thompson,Stanley van den Noort,Brian Y. Weinshenker,Jerry S. Wolinsky +15 more
TL;DR: The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including “monosymptomatic” disease suggestive of MS, disease with a typical relapsing‐remitting course, and disease with insidious progression, without clear attacks and remissions.
Journal ArticleDOI
Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis.
Frederik Barkhof,Massimo Filippi,David Miller,Philip Scheltens,Adriana Campi,Chris H. Polman,Giancarlo Comi,Herman J. Adèr,N. A. Losseff,Jacob Valk +9 more
TL;DR: It is concluded that a four-parameter dichotomized MRI model including gadolinium-enhancement, juxtacortical, infratentorial and periventricular lesions best predicts conversion to clinically definite multiple sclerosis.
Journal ArticleDOI
Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis.
L Fisniku,P A Brex,Daniel R. Altmann,K. A. Miszkiel,C. E. Benton,R. Lanyon,Alan J. Thompson,David Miller +7 more
TL;DR: Lesion volume increases for at least 20 years in relapse-onset multiple sclerosis and the rate of lesion growth is three times higher in those who develop secondary progressive than inThose who remain relapsing remitting multiple sclerosis.
Journal ArticleDOI
A Longitudinal Study of Abnormalities on MRI and Disability from Multiple Sclerosis
TL;DR: In patients who first present with isolated syndromes suggestive of multiple sclerosis, the increases in the volume of the lesions seen on magnetic resonance imaging of the brain in the first five years correlate with the degree of long-term disability from multiple sclerosis.
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