New autoantibody mediated disorders of the central nervous system

Recently, central nervous system disorders have been shown to be associated with autoantibodies. This review summarizes the recent findings and assesses the evidence that these conditions are caused by the antibodies, using the criteria established for peripheral nervous system autoimmune diseases.

Over the last few years, antibodies to voltage-gated calcium and potassium channels, and to glutamate receptors, have been detected in the serum and cerebrospinal fluid of patients with ataxia, limbic encephalitis and certain forms of epilepsy. Some of these patients respond to immunotherapies, suggesting that the antibodies are pathogenic, but there are few demonstrations using the passive transfer approach that antibodies present in the serum can penetrate the blood-brain barrier and affect central nervous system function. Some patients have antibodies to intracellular proteins such as glutamic acid decarboxylase or specific ribonuclear proteins. The pathogenicity of these antibodies must be in some doubt, although intravenous immunoglobulin therapy has been shown to be beneficial in stiff man syndrome, consistent with an autoimmune aetiology for the disease. In only a few conditions, has IgG derived from patients been shown to produce pathogenic effects in vivo or in vitro.

There is much that needs to be done to define the role of these antibodies and to determine how they affect central nervous system function in vivo. These studies must be carried out so that appropriate treatments can be provided for the growing number of patients with possible antibody-mediated conditions.