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The serum and cerebrospinal fluid(CSF)of 8 women with ataxia,6 of whom also had eye movement abnormalities believed to be opsoclonus,were found to contain a highly specific antineuronal antibody we call anti-Ri.Seven of the 8 women also had or developed cancer:carcinoma of the breast in 5, adenocarcinoma in an axillary lymph node in 1,and carcinoma of the fallopian tube in 1.Four patients presented with the neurological disorder;the cancer was diagnosed first in the other 4.Immunohistochemical studies using serum or CSF from all 8 patients revealed a highly specific antibody interaction with central nervous system neuronal nuclei but not with glial or other cells;the titer ranged from 1:5,000 to 1:320,000 in serum and from 1:2,000 to 1:16,000 in CSF.Biotinylated IgG from the patients'serum reacted with the tumors of 3 of 4 patients with anti-Ri antibody but not with breast cancers from patients without anti-Ri antibody.Immunoblots against cerebral cortex neuronal extracts identified protein antigens of 55-kd and 80-kd relative molecular mass.Serum titers by immunoblot ranged from 1:500 to more than 1:40,000 and CSF titers,from 1:10 to 1:2,000.The relative amount of anti-Ri was always higher in CSF than in serum.The antibody was not present in sera from normal individuals;patients with breast cancer without opsoclonus;other patients with opsoclonus;or patients with other paraneoplastic syndromes related to breast,ovarian,or small-cell lung cancer.We conclude that the presence of anti-Ri antibody identifies a subset of patients with paraneoplastic ataxia and eye movement disorders(opsoclonus)who usually suffer from breast or other gynecological cancer;the antibody when present is a useful marker for an underlying malignancy. |
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