New Purkinje cell antibody (PCA-2): marker of lung cancer-related neurological autoimmunity.
Neuron-restricted autoantibodies are important markers of neurological autoimmunity related to cancer. We identified a new paraneoplastic IgG, PCA-2 (Purkinje cell cytoplasmic antibody type 2), in 10 patients. Nine had mixed subacute neurological presentations (5 brainstem or limbic encephalitis, 3 cerebellar ataxia, 2 Lambert-Eaton myasthenic syndrome, 1 autonomic neuropathy, and 1 motor neuropathy). All 9 were smokers, and 8 had definite or probable lung cancer (7 with biopsy-confirmed small cell lung carcinoma [SCLC]; 1 imaged only). One patient had no follow-up information. A 10th patient was among 58 with uncomplicated SCLC. PCA-2 binds to a cytoplasmic antigen in neurons and SCLC cells. Its immunostaining pattern in mouse tissues is distinct from that of the paraneoplastic autoantibodies PCA-1 (anti-Yo, marker of immune response initiated by ovarian or breast carcinoma) and PCA-Tr (anti-Tr, immune response marker of Hodgkin's lymphoma). PCA-2 binds to cerebellar Purkinje somata and dendrites, neurons in internal granular layer and dentate nucleus, and neuronal elements in gut and kidney. Western blots of reduced/denatured cerebellar and SCLC proteins reveal a common antigenic band, of approximately 280 kd. PCA-2 is the seventh IgG neuronal autoantibody marker of paraneoplastic autoimmunity identifiable unambiguously by standardized immunofluorescence criteria.
Vernino
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Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Lennon
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VA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D015415:Biomarkers; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011689:Purkinje Cells / Q000276:immunology* / Q000473:pathology*
D000906:Antibodies; D015415:Biomarkers