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Summary
Multiple sclerosis is a chronic inflammatory disease of the white and grey matter
which results in irrevocable axonal and neuronal damage. Grey matter injury is widespread
and reflects disability to a greater extent than do white matter lesions. Growing
understanding of the immunopathology of multiple sclerosis is leading the way to the
identification and testing of untapped targets that may offer new and more specific
ways to treat the disease. For example, data from animal models support a two-step
pathological process in multiple sclerosis, whereby T cells initially induce inflammation
and open up the blood–brain barrier, which then allows access to antibodies which
aggravate tissue damage. Determination of the specificity of the invading T cells
and the autoantibodies that cause disease is a major focus of current research. The
discovery of anti-aquaporin-4 autoantibodies in patients with neuromyelitis optica
and of anti-MOG antibodies in a subset of children with paediatric autoimmune demyelinating
disease are promising steps in this direction. Recently, the axoglial antigens neurofascin
and contactin-2/TAG-1, which are localised around the node of Ranvier, were identified
as targets of an autoimmune response in multiple sclerosis. Such an autoimmune response
might induce axonal injury and direct the immunopathological response to the grey
matter. It is to be hoped that the outcome of such investigations will lead to the
identification of patient subgroups based on their autoreactivity and new ways to
treat them safely and effectively.
Keywords
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© 2011 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
