[Pathogenesis of paraneoplastic neurological syndromes].
Paraneoplastic neurological syndromes (PNS) are thought to be caused by autoimmune processes triggered by the cancer and directed against antigens common to both the cancer and the nervous system. There are several clinical phenotypes in combinations with the neurological syndromes, origin of cancer and the specific autoantibodies. PNS with antibodies against channel receptors on the cell surface tend to respond favorably to antibody-depletion therapies; this suggests that the antibodies detected in these PNS groups are closely related to their pathogenesis. PNS having the antibodies against intracellular proteins might be caused by cytotoxic T cell-mediated cell death. This is because the following findings; 1) the prominent mononuclear cells in CSF, 2) the infiltration of inflammatory cells, mainly CD8+ T lymphocytes, in the tumor and the nervous tissue. In addition, T cell receptor usage of infiltrated T lymphocytes in the affected CNS lesions has been shown to be oligoclonal. We observed that the disease model could not be produced using only anti-intracellular antibodies such as anti-Yo or anti-Hu antibodies, but that CTL activity could be induced in CD8+ T cells isolated from the peripheral mononuclear cells obtained from PNS patients with anti-Yo or anti-Hu antibodies. The anti-Yo- or anti-Hu-antibody-positive patients possess common human leukocyte antigen (HLA) class I motifs. This implies that in patients with anti-Yo or anti-Hu antibodies, the presentation of the certain antigen peptides on the cell surface could be used to stimulate CD8+ T lymphocytes that could attack their target tissues as effectors. Antigen-specific CTL-mediated cell death has been observed in cancer immunology and PNS appears to be a potential candidates for a future CTL-mediated neurological disease model.
Tanaka
Keiko
K
Department of Neurology, Kanazawa Medical University, 1-1 Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan.
D001323:Autoantibodies; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016923:Cell Death; D051959:ELAV Proteins; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000276:immunology; D009420:Nervous System / Q000276:immunology; D020361:Paraneoplastic Syndromes, Nervous System / Q000276:immunology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D001323:Autoantibodies; C095184:CDR2 protein, human; D051959:ELAV Proteins; D009419:Nerve Tissue Proteins