Tuesday, 10 March 2015

Biomarkers of Nerve Damage and progression

Hinsinger G, Galéotti N, Nabholz N, Urbach S, Rigau V, Demattei C, Lehmann S, Camu W, Labauge P, Castelnovo G, Brassat D, Loussouarn D, Salou M, Laplaud D, Casez O, Bockaert J, Marin P, Thouvenot E. Chitinase 3-like proteins as diagnostic and prognostic biomarkers of multiple sclerosis. Mult Scler. 2015. pii: 1352458514561906. [Epub ahead of print]

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.

Yesterday we heard of a marker CHI3L1 that was associated with progression and today we hear the same thing. There is more of the same in another paper and again the work of ProfG is replicated
They said "If replicated in future studies, serum NfL may represent a reliable and easily accessible biomarker of early axonal damage in CIS and MS". They didn't have to wait long for a replication....i.e. about a week.

Modvig S, Degn M, Roed H, Sørensen T, Larsson H, Langkilde A, Frederiksen J, Sellebjerg F. Cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain predict multiple sclerosis development and disability after optic neuritis. Mult Scler. 2015. pii: 1352458515574148. [Epub ahead of print]

BACKGROUND:Cerebrospinal fluid (CSF) biomarkers have been suggested to predict multiple sclerosis (MS) after clinically isolated syndromes, but studies investigating long-term prognosis are needed.
OBJECTIVE:To assess the predictive ability of CSF biomarkers with regard to MS development and long-term disability after optic neuritis (ON).
METHODS:Eighty-six patients with ON as a first demyelinating event were included retrospectively. Magnetic resonance imaging (MRI), CSF leukocytes, immunoglobulin G index and oligoclonal bands were registered. CSF levels of chitinase-3-like-1, osteopontin, neurofilament light-chain, myelin basic protein, CCL2, CXCL10, CXCL13 and matrix metalloproteinase-9 were measured by enzyme-linked immunosorbent assay. Patients were followed up after 13.6 (range 9.6-19.4) years and 81.4% were examined, including Expanded Disability Status Scale and MS functional composite evaluation. 18.6% were interviewed by phone.
RESULTS:Forty-six (53.5%) developed clinically definite MS (CDMS) during follow-up. In a multivariate model MRI (p=0.0001), chitinase 3-like 1 (p=0.0033) and age (p=0.0194) combined predicted CDMS best. Neurofilament light-chain predicted long-term disability by the multiple sclerosis severity scale (p=0.0111) and nine-hole-peg-test (p=0.0202). Chitinase-3-like-1 predicted long-term cognitive impairment by the paced auditory serial addition test (p=0.0150).
CONCLUSION: Neurofilament light-chain and chitinase-3-like-1 were significant predictors of long-term physical and cognitive disability. Furthermore, chitinase-3-like-1 predicted CDMS development. Thus, these molecules hold promise as clinically valuable biomarkers after ON as a first demyelinating event.

Another study detecting chitinase-3-like-1 activity


  1. Mouse,

    What do these findings practically mean for someone with MS? Will the biomarkers be used just in trials or for individual patients to monitor their disease (instead of MRI)?

    1. In the short term I think it adds more and more weight that Neurofilaments are a tool to monitor nerve damage. These can be an outcome marker, but it would need some work up to make a quick test for every day use. Also if you find high neurofilament levels what are you going to do, get more anti-inflammatories but we dont have licenced neuroprotectors available yet


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