Anti-amphiphysin I antibodies in patients with paraneoplastic neurological disorders associated with small cell lung carcinoma

摘要

Patients with stiff man syndrome and breast cancer developanti-amphiphysin I antibodies that primarily recognise the C terminus of the protein. Anti-amphiphysin I antibodies have also beenidentified in a few patients with paraneoplastic neurological disorders(PND) and small cell lung cancer (SCLC). The frequency ofanti-amphiphysin I antibodies in patients with SCLCand PND was analysed and the epitope specificity of these antibodieswas characterised.
 Anti-amphiphysin I antibodies were evaluated byimmunohistochemistry on human and rat cerebellum and immunoblots ofrat 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 sampleswere confirmed with immunoblots of recombinant human amphiphysin I andimmunoreacted with five overlapping peptide fragments covering the fulllength of the molecule.
 Serum samples positive foranti-amphiphysin I antibodies included those fromseven (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 onehad anti-Hu-antibodies but no detectable tumour. The PND includedencephalomyelitis/sensory neuropathy (five patients), cerebellardegeneration (one), and opsoclonus (one). Allanti-amphiphysin I antibodies reacted with the Cterminus of amphiphysin I, but seven also recognised other fragments ofthe molecule.
 In conclusion, anti-amphiphysin I antibodies are present atlow frequency in patients with SCLC irrespective of the presence of anassociated PND. All anti-amphiphysin Iantibody positive serum samples have in common reactivity with the Cterminus of the protein.