Anti-amphiphysin I antibodies in patients with paraneoplastic neurological disorders associated with small cell lung carcinoma
- aService of Neurology and Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona. Spain, bDepartment of Neurology, Memorial Sloan-Kettering Cancer Center, New York, USA, cDepartment of Cell Biology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Conn, USA, dService of Neurology, Hôpital de la Pitié-Salpêtrière, INSERM U134, Paris, France
- Dr Francesc Graus, Servei de Neurologia, Hospital Clínic, Villarroel 170, Barcelona 08036. Spain. Telephone 0034 3 2272213; fax 0034 3 2275414; emailgraus{at}medicina.ub.es
- Received 9 March 1998
- Revised 3 September 1998
- Accepted 11 September 1998
Abstract
Patients with stiff man syndrome and breast cancer develop anti-amphiphysin I antibodies that primarily recognise the C terminus of the protein. Anti-amphiphysin I antibodies have also been identified in a few patients with paraneoplastic neurological disorders (PND) and small cell lung cancer (SCLC). The frequency of anti-amphiphysin I antibodies in patients with SCLC and PND was analysed and the epitope specificity of these antibodies was characterised.
Anti-amphiphysin I antibodies were evaluated by immunohistochemistry on human and rat cerebellum and immunoblots of rat brain homogenates. Serum samples included 134 patients with PND and anti-Hu antibodies (83% had SCLC), 44 with SCLC and PND without antiHu-antibodies, 63 with PND and either Yo, Ri, or Tr antibodies, 146 with SCLC without PND, and 104 with non-PND. Positive serum samples were confirmed with immunoblots of recombinant human amphiphysin I and immunoreacted with five overlapping peptide fragments covering the full length of the molecule.
Serum samples positive for anti-amphiphysin I antibodies included those from seven (2.9%) patients with PND and two (1.4%) with SCLC without PND. Six of the seven anti-amphiphysin I antibody positive patients with PND had SCLC (three with Hu-antibodies), and one had anti-Hu-antibodies but no detectable tumour. The PND included encephalomyelitis/sensory neuropathy (five patients), cerebellar degeneration (one), and opsoclonus (one). All anti-amphiphysin I antibodies reacted with the C terminus of amphiphysin I, but seven also recognised other fragments of the molecule.
In conclusion, anti-amphiphysin I antibodies are present at low frequency in patients with SCLC irrespective of the presence of an associated PND. All anti-amphiphysin I antibody positive serum samples have in common reactivity with the C terminus of the protein.
