Relationship between Cerebrospinal Fluid Biomarkers for Inflammation, Demyelination and Neurodegeneration in Acute Optic NeuritisReportar como inadecuado




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Background

Various inflammatory biomarkers show prognostic potential for multiple sclerosis MS-risk after clinically isolated syndromes. However, biomarkers are often examined singly and their interrelation and precise aspects of their associated pathological processes remain unclear. Clarification of these relationships could aid the appropriate implementation of prognostic biomarkers in clinical practice.

Objective

To investigate the interrelation between biomarkers of inflammation, demyelination and neurodegeneration in acute optic neuritis and to assess their association to measures of MS risk.

Material and Methods

A prospective study at a tertiary referral centre from June 2011 to December 2012 of 56 patients with optic neuritis as a first demyelinating symptom and 27 healthy volunteers. Lumbar puncture was performed within 28 median 16 days of onset. CSF levels of CXCL13, matrix metalloproteinase MMP-9, CXCL10, CCL-2, osteopontin and chitinase-3-like-1, myelin basic protein MBP and neurofilament light-chain NF-L were determined. MS-risk outcome measures were dissemination in space DIS of white matter lesions on cerebral MRI, CSF oligoclonal bands and elevated IgG-index.

Results

In the interrelation analysis the biomarkers showed close correlations within two distinct groups: Biomarkers of leukocyte infiltration CXCL13, MMP-9 and CXCL10 were strongly associated p<0.0001 for all. Osteopontin and chitinase-3-like-1 were also tightly associated p<0.0001 and correlated strongly to tissue damage markers NF-L and MBP. The biomarkers of leukocyte infiltration all associated strongly with MS-risk parameters, whereas CHI3L1 and MBP correlated with MRI DIS, but not with CSF MS-risk parameters and osteopontin and NF-L did not correlate with any MS-risk parameters.

Conclusions

Our findings suggest two distinct inflammatory processes: one of leukocyte infiltration, represented by CXCL13, CXCL10 and MMP-9, strongly associated with and potentially predicting MS-risk; the other represented by osteopontin and CHI3L1, suggesting tissue damage-related inflammation, potentially predicting residual disabilities after attack and perhaps cumulative damage over time. These hypotheses should be further addressed in follow-up studies.



Autor: Signe Modvig , Matilda Degn, Henrik Horwitz, Stig P. Cramer, Henrik B. W. Larsson, Benedikte Wanscher, Finn Sellebjerg, Jette L.

Fuente: http://plos.srce.hr/



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