Abstract Details

Title CSF Immunological Biomarkers Associated with Axonal Damage in Multiple Sclerosis

Topic MS and Related Diseases

Presentation(s) P03 - (-)

Poster/Presentation
Number 237

Objective

Background BACKGROUND: High CSF levels of neurofilaments reflect axonal loss and neurodegeneration in MS, being markers of disease progression. It has been proposed that NfL can reflect acute axonal damage mediated by inflammatory mechanisms. In a cross-sectional study we studied clinical, MRI and CSF data that associate with increased NfL levels. It may provide new insights on MS pathogenesis and therapeutic targets.

Design/Methods DESIGN/METHODS: Serum and CSF samples were obtained after informed consent from 64 patients with multiple sclerosis as part of their clinical workup and 17 patients with other neurological non-inflammatory diseases (OND). CSF samples were centrifuged and the cellular pellet processed by cytometry (FACSCanto II. Becton Dickinson). Oligoclonal bands (OCB) were studied by isoelectric focusing and immunoblotting. NfL levels were quantified with the Uman diagnostic test. Association of MS activity, MRI and CSF findings with NfL levels were analyzed.

Results RESULTS: NfL levels were higher in MS than in OND (3605±712.1 vs 300.1±218.8 ng/l, p<0.0001). MS patients were divided in two groups according to CSF NfL levels. Patients with CSF NfL above the cut-off value of 870 ng/l (M+2.6 SD of OND group) associated with higher relapse rate (2.32±1.38 vs 1.38±0.19, p=0.0003), EDSS (2.34±0.22 vs 1.39±0.19, p=0,0051) and T2 lesion number (22.38±2.59 vs 13.05±14.30, p=0.0019) than patients with lower CSF NfL. CD5+B lymphocytes were elevated in MS patients with high NFL levels (p=0.002). CD4+ and CD8+ cells did not differ according to these levels. High NfL were significantly associated with the presence of oligoclonal IgM bands (produced by CD5+ B cells)(p=0.0015).

Conclusions CONCLUSIONS: Axonal loss reflected by increased CSF NfL associates with oligoclonal IgM bands and increased CSF CD5+B lymphocytes in MS.

Authors/Disclosures
Luisa M. Villar (Hospital Ramon Y Cajal) PRESENTER	Luisa M. Villar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Luisa M. Villar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol-Myers Squibb. Luisa M. Villar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Luisa M. Villar has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Luisa M. Villar has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Luisa M. Villar has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Luisa M. Villar has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Luisa M. Villar has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol-Myers Squibb. The institution of Luisa M. Villar has received research support from European Union. The institution of Luisa M. Villar has received research support from Instituto de Salud Carlos III (Spanish Goverment).
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Winston Ko (Genervon Biopharmaceuticals)	No disclosure on file
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