Quantified CSF antibody reactivity against myelin in multiple sclerosis.

Abstract

Synthesis of clonal IgG is a consistent feature of patients with multiple sclerosis (MS). Whether oligoclonal bands (OCBs) represent unspecific disease bystanders or active components in MS pathology is an open question. The aim of this study was to develop a method to quantify and compare the reactivity of cerebrospinal fluid (CSF) antibodies from patients with and without MS. We collected CSF from 262 patients from two different cohorts, which included 148 patients with MS and 114 with other neurological diseases (OND). We established a highly sensitive electrochemiluminescence (ECL)-based assay to measure CSF antibody reactivity against purified myelin particles and biotin anchored liposomes. The diagnostic value of the ECL score against myelin particles was assessed with receiver operating characteristic curves. CSF from patients with MS have higher reactivity toward purified myelin particles as compared to those with OND with OCBs. Using liposomes with defined lipid compositions and myelin particles from ceramide synthase 2 (CerS2) knockout mice, we find that some of the CSF antibody reactivity is directed against cerebrosides. The ECL-based assay system expands the currently available toolbox for the detection of autoantibodies in MS and related diseases.