title: Antiamphiphysin antibodies with small-cell lung carcinoma and paraneoplastic encephalomyelitis.
abstract: Paraneoplastic encephalomyelitis developed as the presenting feature of small-cell lung carcinoma in 3 patients. Two patients with paraneoplastic encephalomyelitis manifested predominantly as subacute sensory neuronopathy did not improve after prednisone treatment and chemotherapy. The third patient had severe axial and limb rigidity and myoclonus, which partially improved after chemotherapy and treatment with intravenous immunoglobulin and prednisone. Serum from each patient immunocytochemically stained the neuropil and to a lesser degree the neuronal cytoplasm in human cerebral and cerebellar cortex. On immunoblots of human neuronal extracts, each patient's serum contained high-titer IgG antibodies reacting with a protein band of apparent molecular mass 125 kd. This autoantibody pattern is indistinguishable from antibodies recently identified in several women with breast carcinoma and stiff-man syndrome. Screening of a human brain complementary DNA expression library with patient serum yielded clones whose sequence is identical to that of the synaptic vesicle-related protein amphiphysin. Reverse transcriptase-polymerase chain reaction demonstrated expression of amphiphysin in 8 of 10 small-cell lung carcinomas and in 5 of 14 breast carcinomas. These observations highlight the clinical and serological heterogeneity of paraneoplastic central nervous system disorders: Patients with a given clinical syndrome may have different antineuronal antibodies, and patients with a given autoantibody specificity have differing clinical presentations.
authors.affiliation: Department of Neurology, Indiana University Medical Center, Indianapolis 46202-5111, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Dropcho
mesh_terms: D000368:Aged; D000974:Antibodies, Antinuclear / Q000032:analysis; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D018288:Carcinoma, Small Cell / Q000150:complications / Q000276:immunology*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D004679:Encephalomyelitis / Q000150:complications / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000150:complications / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000276:immunology*; D010257:Paraneoplastic Syndromes / Q000150:complications / Q000276:immunology*; D016133:Polymerase Chain Reaction; D016750:Stiff-Person Syndrome / Q000209:etiology / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; C075637:amphiphysin