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Antiamphiphysin Antibodies Are Associated With Various Paraneoplastic Neurological Syndromes and Tumors
Jean Christophe Antoine, MD;
Lena Absi, PhD;
Jerome Honnorat, MD;
Jean-Marc Boulesteix, MD;
Thomas de Brouker, MD;
Christophe Vial, MD;
Margareth Butler, PhD;
Pietro De Camilli, PhD;
Daniel Michel, MD
Arch Neurol. 1999;56:172-177.
Background Antiamphiphysin antibodies react with a 128-kd protein found in synaptic vesicles.They were first described in patients with paraneoplastic stiff-man syndrome and breast cancer, but studies suggest that they can also occur in patients with other tumors and neurological disorders.
Objective To determine if antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors.
Patients and Methods Of 2800 serum samples tested by routine immunohistochemical procedures on sections of paraformaldehyde-fixed rat brain for the detection of autoantibodies associated with paraneoplastic neurological syndromes, 5 were selected because of labeling suggestive of antiamphiphysin antibodies and subsequently confirmed by the results of Western blot analysis using recombinant amphiphysin protein. Controls consisted of 40 patients with various nonparaneoplastic neurological diseases; 101 patients with cancer but without paraneoplastic neurological syndrome; 9 patients with small cell lung cancer, anti-Hu antibodies, and paraneoplastic neurological syndrome; 3 patients with M2-type antimitochondrial antibodies but no neurological disorder; and 30 normal subjects.
Results Of the 5 patients with antiamphiphysin antibodies, patient 1 had sensory neuronopathy, encephalomyelitis, and breast cancer; patient 2 had limbic encephalitis, and small cell lung cancer was detected in the mediastinum after 24 months of follow-up; patient 3 had encephalomyelitis and ovarian carcinoma; and patients 4 and 5 had Lambert-Eaton myasthenic syndrome and small cell lung cancer (patient 4 subsequently developed cerebellar degeneration). None of the 5 had stiffness. Two patients (Nos. 2 and 4) had antimitochondrial antibodies. The two patients (Nos. 4 and 5) with Lambert-Eaton myasthenic syndrome had antibodies directed against the voltage-gated calcium channel, and patient 2 subsequently developed anti-Hu antibodies. In the controls, antiamphiphysin antibodies were detected by Western blot analysis in 3 of 8 patients with anti-Hu antibodies, but in none of the other groups.
Conclusions These data indicate that antiamphiphysin antibodies are not specific for one type of tumor or one neurological syndrome and can be associated with other neural and nonneural antibodies. The simultaneous association of several antibodies in some patients suggests multimodal autoantibody production.
From the Neurology Service, Hôpital de Bellevue, Saint-Etienne (Drs Antoine and Michel), Hôpital Neurologique, Lyon (Dr Honnorat), Centre Hospitalier, Cahors (Dr Boulesteix), and Hôpital de la Fontaine, Saint-Denis (Dr de Brouker), France; the Centre de Transfusion Sanguine, Saint-Etienne (Dr Absi); the Electromyography Service, Hôpital Neurologique, Lyon (Dr Vial); and the Department of Cell Biology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Conn (Drs Butler and De Camilli).
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