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Autoantibodies in paraneoplastic neurological syndrome.

Paraneoplastic neurological syndrome is a rare disorder caused by the secondary effects of cancer and is thought to be immune-mediated. A high titer of autoantibodies in the patient's serum and cerebrospinal fluid, directed against both neurons and tumor, have been detected in some forms of this syndrome. These autoantibodies are considered the result of an immunological response to tumor and may cross-react with cells of the nervous system, causing neuronal damage. Specific forms of this syndrome are often associated with specific antineuronal antibodies and tumors. The onset of neurological symptoms and detection of these antibodies often precede the diagnosis of the tumor; therefore, detection of these antibodies greatly assists the diagnosis of this syndrome and prompts investigations for the underlying tumor. The pathogenicity of these antineuronal antibodies has been proven in only a few cases, such as that of anti-voltage gated calcium-channel antibodies in Lambert-Eaton myasthenic syndrome. The selective involvement of specific types of neurons has not been fully elucidated. The target spectrum of some of these antineuronal antibodies correlates well with the neurological symptoms, but that of others is wider than expected from the symptoms. Interesting evidence has suggested that these antionconeuronal antibodies can suppress tumor growth. The discovery of new antibodies and characterization of target molecules have been reported with advances in the field of molecular biology. A more detailed understanding of the relationship between the cancer and the neural involvement from the molecular biological standpoint may lead to rational tumor therapy and elucidation of the mechanism of neuronal death. Here, major clinical forms with well-known antineuronal antibodies and specific tumors are reviewed; for each antineuronal antibody, the target antigens and its putative role in the pathogenesis of this syndrome are described.

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