Cerebrospinal fluid immunological biomarkers associated with axonal damage in multiple sclerosis

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 .