Anti-amphiphysin antibodies

Synonyms: Anti-amphiphysin I antibodies

Clinical associations: Stiff-person syndrome associated with breast cancer. Same syndromes associated with anti-Hu antibodies (Paraneoplastic encephalomyelitis/ sensory neuronopathy) when the underlying tumor is a small-cell lung carcinoma (SCLC)

Tumor associations: Breast cancer or small-cell lung cancer (SCLC).

Frequency of anti-amphiphysin antibodies in patients with suspected paraneoplastic neurological syndromes (PNS) without evidence of cancer: 5% (one patient reported out of 20)

Frequency of anti-amphiphysin antibodies in patients with cancer without PNS: 1% in a series of 146 patients with SCLC. No cases reported in 55 patients with breast or other gynecological tumors.

Screening test:
Immunohistochemistry on frozen rat or mouse cerebellar sections (figure 1).

Figure 1. Anti-amphiphysin immunoreactivity detected by immunofluoresce on rat cerebellum. Notice that cytoplasm of Purkinje cells is negative.

Confirmatory test:
Several commercial tests using immunoblots of recombinant amphiphysin protein. Immunoblot of extracts of rat brain (figure 2)

Figure 2. Immunoblot of rat brain extracts probed with anti-amphiphysin positive serum (lanes 2-6) immunoreact with a band of 128 Kd of approximate molecular mass (long arrow). Some sera also present anti-Hu antibodies. Lanes 7 and 8 probed with serum with anti-Hu antibodies. Negative controls in lanes 1 and 9,10.

Immunologic associations:
Patients with paraneoplastic syndromes, anti-amphiphysin antibodies, and SCLC may also harbor anti-Hu antibodies.

Amphiphysin
Amphiphysin belongs to the BAR (Bin-Amphiphysin-Rsvsp) family proteins. There are two isoforms, amphiphysin I and II. Amphiphysin I is the antigen recognized by anti-amphiphysin antibodies that occur in paraneoplastic neurological syndromes. Amphiphysin I is a presynaptic protein that play a key role in clathrin-mediated endocytosis of synaptic vesicles released in the presynaptic terminals.

References

1. Antoine JC, Absi L, Honnorat J, et al. Antiamphiphysin antibodies are associated with various paraneoplastic neurological síndromes and tumors. Arch Neurol 1999;56:172-7.
2. Folli F, Solimena M, Cofiell R, et al. Autoantibodies to a 128-kd synaptic protein in three women with the stiff-man syndrome and breast cancer. N Engl J Med 1993;328:546-51.
3. Prego L, Previtali SC, Nemni R, et al. Autoantibodies to amphiphysin I and amphiphysin II in a patient with sensory-motor neuropathy. Eur Neurol 2002;47:196-200.
4. Saiz A, Dalmau J, Butler MH, et al. Anti-amphiphysin I antibodies in patients with paraneoplastic neurologic disorders associated with small cell lung carcinoma. J Neurol Neurosurg Psychiatry 1999;66:214-7.
5. Zhang B, Zelhof AC. Amphiphysins: Rasing the BAR for synaptic vesicle recycling and membrane dynamics. Traffic 2002;3:542-60.

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