Autoimmunity to gephyrin in Stiff-Man syndrome.

Abstract

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.

• Authors: M H Butler, A Hayashi, N Ohkoshi, C Villmann, C M Becker, G Feng, P De Camilli, M Solimena
• Journal: Neuron (Neuron) Vol. 26 Issue 2 Pg. 307-12 (May 2000) ISSN: 0896-6273 [Print] United States
• PMID: 10839351 (Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Autoantibodies
• Carrier Proteins
• Membrane Proteins
• gephyrin

Topics

• Animals
• Autoantibodies (analysis)
• Autoimmunity
• CHO Cells
• Carrier Proteins (immunology)
• Cricetinae
• Humans
• Male
• Mediastinal Neoplasms (complications)
• Membrane Proteins (immunology)
• Middle Aged
• Molecular Sequence Data
• Stiff-Person Syndrome (complications, immunology, physiopathology)