TY - JOUR
T1 - The synaptic vesicle-associated protein amphiphysin is the 128-kd autoantigen of stiffman syndrome with breast cancer
AU - Camilli, Pietro De
AU - Thomas, Annette
AU - Cofiell, Roxanne
AU - Folli, Franco
AU - Lichte, Beate
AU - Piccolo, Giovanni
AU - Meinck, Hans Michael
AU - Austoni, Mario
AU - Fassetta, Giuliano
AU - Bottazzo, Gianfranco
AU - Bates, David
AU - Cartlidge, Niall
AU - Solimena, Michele
AU - Kilimann, Manfred W.
PY - 1993/12/1
Y1 - 1993/12/1
N2 - Stiff-Man syndrome (SMS) is a rare disease of the central nervous system (CNS) characterized by progressive rigidity ofthe 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 rytoplasmic proteins associated with synaptic vesicles and SMS.
AB - Stiff-Man syndrome (SMS) is a rare disease of the central nervous system (CNS) characterized by progressive rigidity ofthe 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 rytoplasmic proteins associated with synaptic vesicles and SMS.
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U2 - 10.1084/jem.178.6.2219
DO - 10.1084/jem.178.6.2219
M3 - Article
C2 - 8245793
AN - SCOPUS:0027517423
VL - 178
SP - 2219
EP - 2223
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 6
ER -