Autoimmunity to gephyrin in Stiff-Man syndrome.
Stiff-Man syndrome (SMS) is a rare disease of the central nervous system (CNS) characterized by chronic rigidity, spasms, and autoimmunity directed against synaptic antigens, most often the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). In a subset of cases, SMS has an autoimmune paraneoplastic origin. We report here the identification of high-titer autoantibodies directed against gephyrin in a patient with clinical features of SMS and mediastinal cancer. Gephyrin is a cytosolic protein selectively concentrated at the postsynaptic membrane of inhibitory synapses, where it is associated with GABA(A) and glycine receptors. Our findings provide new evidence for a close link between autoimmunity directed against components of inhibitory synapses and neurological conditions characterized by chronic rigidity and spasms.
Butler
M H
MH
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Hayashi
A
A
Ohkoshi
N
N
Villmann
C
C
Becker
C M
CM
Feng
G
G
De Camilli
P
P
Solimena
M
M
D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D015551:Autoimmunity; D016466:CHO Cells; D002352:Carrier Proteins / Q000276:immunology*; D006224:Cricetinae; D006801:Humans; D008297:Male; D008479:Mediastinal Neoplasms / Q000150:complications; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016750:Stiff-Person Syndrome / Q000150:complications / Q000276:immunology* / Q000503:physiopathology
D001323:Autoantibodies; D002352:Carrier Proteins; D008565:Membrane Proteins; C073441:gephyrin