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Cerebrospinal fluid immunological biomarkers associated with axonal damage in multiple sclerosis
Author(s) -
Villar L. M.,
Picón C.,
CostaFrossard L.,
Alenda R.,
GarcíaCaldentey J.,
Espiño M.,
Muriel A.,
ÁlvarezCermeño J. C.
Publication year - 2015
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.12579
Subject(s) - cerebrospinal fluid , multiple sclerosis , medicine , neurodegeneration , pathology , biomarker , atrophy , magnetic resonance imaging , clinically isolated syndrome , neuromyelitis optica , antibody , immunology , biology , disease , biochemistry , radiology
Background and purpose Cerebrospinal fluid ( CSF ) neurofilament light protein ( NFL ) is a promising biomarker of axonal injury and neurodegeneration. Here CSF lymphocyte subpopulations and antibodies, potential players of neurodegeneration, are examined in relation to CSF NFL shedding in MS . Methods Cerebrospinal fluid NFL from 127 consecutive untreated MS patients was analysed. Samples from 37 age‐matched patients with other central nervous system non‐inflammatory neurological diseases ( NIND ) were also assessed. CD 4+, CD 8+, CD 56+ and CD 19+ cell subsets were studied by flow cytometry. Oligoclonal I g G and I g M bands ( OCMB ) against lipids were studied by isoelectric focusing and immunoblotting. These data were analysed in relation to clinical and magnetic resonance imaging features. Results A CSF NFL cut‐off value of 900 ng/l (mean + 3 SD of NIND values) was calculated. MS patients with increased NFL values showed significantly higher Multiple Sclerosis Severity Score and magnetic resonance imaging lesion number. The presence of OCMB ( P < 0.0001) and elevated T and B lymphocyte counts was associated with increased levels of CSF NFL . Conclusions High CSF NFL levels are associated with elevated CSF lymphocyte cell counts and intrathecal synthesis of I g M against lipids. These findings support a role for OCMB in the axonal damage of MS offering a rationale for the association of these antibodies with disability and brain atrophy progression in MS .