Anti-Ri: an antibody associated with paraneoplastic opsoclonus and breast cancer.
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.
Luque
F A
FA
Department of Neurology, Neuro-Oncology Memorial Sloan-Kettering Cancer Center, New York, NY.
Furneaux
H M
HM
Ferziger
R
R
Rosenblum
M K
MK
Wray
S H
SH
Schold
S C
SC
Glantz
M J
MJ
Jaeckle
K A
KA
Biran
H
H
Lesser
M
M
D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid; D000912:Antibodies, Neoplasm / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000175:diagnosis*; D002540:Cerebral Cortex / Q000276:immunology; D005133:Eye Movements; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009474:Neurons / Q000276:immunology*; D010257:Paraneoplastic Syndromes / Q000175:diagnosis*
D000888:Antibodies, Anti-Idiotypic; D000912:Antibodies, Neoplasm