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Brain Advance Access originally published online on December 8, 2003
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Brain, Vol. 127, No. 2, 269-279, 2004
© 2004 Guarantors of Brain
doi: 10.1093/brain/awh031

Serum autoantibodies to cell surface determinants in multiple sclerosis: a flow cytometric study

Oliver Lily*, Jacqueline Palace and Angela Vincent

1 Neurosciences Group, Weatherall Institute of Molecular Medicine, Department of Clinical Neurology, University of Oxford *Present address: Department of Neurology, Leeds General Infirmary, Leeds, UK

Correspondence to: Angela Vincent, Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK E-mail: angela.vincent{at}imm.ox.ac.uk

Multiple sclerosis is thought to be an autoimmune, inflammatory, cell-mediated disease. However, there is evidence suggesting that autoantibodies could play a role in the pathogenesis of multiple sclerosis. Many studies have looked for antibodies to candidate antigens such as myelin basic protein or myelin-oligodendrocyte glycoprotein, with inconclusive results. In order to determine whether antibodies to cell surface determinants on oligodendrocyte or neuronal cells were present in multiple sclerosis, we used flow cytometry to detect antibody binding to intact cultured human cell lines, comparing sera from multiple sclerosis patients with sera from patients with other inflammatory CNS diseases. Sera from healthy individuals were used to determine a normal range. Significant surface binding of IgG or IgM antibodies to oligodendrocyte precursor (OPC)-derived cell lines was seen in 50% of multiple sclerosis sera with no significant difference between secondary progressive (SPMS) and relapsing–remitting (RRMS) subgroups. In contrast, binding to a neuronal cell line, SK-N-SH, was seen with 70% of SPMS sera compared with 25% of RRMS sera (P < 0.001). No significant difference in antibody binding between multiple sclerosis sera and control sera was seen when OPCs were differentiated or when the cells were permeabilized to expose intracellular antigens. Results from all nine patients with ‘benign’ multiple sclerosis were indistinguishable from controls. This study represents a systematic approach to begin to define new antigenic targets in multiple sclerosis and demonstrates that antibodies to accessible antigens on the cell surface of both OPCs and neurons are present in some patients. The results lend support to the possibility that autoantibody-mediated processes are important in a subgroup of multiple sclerosis patients. Identification of the cell surface determinants to which the antibodies bind may shed light on new targets for therapeutic intervention.

Key Words: multiple sclerosis; autoantibodies; flow cytometry; neuroblastoma cells; oligodendrocyte precursor cells

Abbreviations: ADEM= acute disseminated encephalomyelitis; ECACC = European Collection of Cell Cultures; EDSS = Expanded Disability Status Score; FACS = fluorescence-activated cell sorter; OPC = oligodendrocyte precursor cell; PDGF = platelet-derived growth factor; RRMS = relapsing–remitting multiple sclerosis; SPMS = secondary progressive multiple sclerosis

Received July 15, 2003. Accepted August 27, 2003.


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