title: The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man syndrome with breast cancer.
abstract: Stiff-Man syndrome (SMS) is a rare disease of the central nervous system (CNS) characterized by progressive rigidity of the body musculature with superimposed painful spasms. An autoimmune origin of the disease has been proposed. In a caseload of more than 100 SMS patients, 60% were found positive for autoantibodies directed against the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). Few patients, all women affected by breast cancer, were negative for GAD autoantibodies but positive for autoantibodies directed against a 128-kD synaptic protein. We report here that this antigen is amphiphysin. GAD and amphiphysin are nonintrinsic membrane proteins that are concentrated in nerve terminals, where a pool of both proteins is associated with the cytoplasmic surface of synaptic vesicles. GAD and amphiphysin are the only two known targets of CNS autoimmunity with this distribution. This finding suggests a possible link between autoimmunity directed against cytoplasmic proteins associated with synaptic vesicles and SMS.
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: P
authors.initials: P
authors.lastname: De Camilli
authors.forename: A
authors.initials: A
authors.lastname: Thomas
authors.forename: R
authors.initials: R
authors.lastname: Cofiell
authors.forename: F
authors.initials: F
authors.lastname: Folli
authors.forename: B
authors.initials: B
authors.lastname: Lichte
authors.forename: G
authors.initials: G
authors.lastname: Piccolo
authors.forename: H M
authors.initials: HM
authors.lastname: Meinck
authors.forename: M
authors.initials: M
authors.lastname: Austoni
authors.forename: G
authors.initials: G
authors.lastname: Fassetta
authors.forename: G
authors.initials: G
authors.lastname: Bottazzo
authors.forename: D
authors.initials: D
authors.lastname: Bates
authors.forename: N
authors.initials: N
authors.lastname: Cartlidge
authors.forename: M
authors.initials: M
authors.lastname: Solimena
authors.forename: M W
authors.initials: MW
authors.lastname: Kilimann
mesh_terms: D001324:Autoantigens / Q000737:chemistry*; D001327:Autoimmune Diseases / Q000276:immunology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000276:immunology*; D005260:Female; D006801:Humans; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000276:immunology*; D016750:Stiff-Person Syndrome / Q000276:immunology*; D014018:Tissue Distribution
chemical_list: D001324:Autoantigens; D009419:Nerve Tissue Proteins; C075637:amphiphysin