Autoantibodies to GABA-ergic neurons and pancreatic beta cells in stiff-man syndrome.
Stiff-man syndrome is a rare disorder of the central nervous system of unknown pathogenesis. We have previously reported the presence of autoantibodies against glutamic acid decarboxylase (GAD) in a patient with stiff-man syndrome, epilepsy, and insulin-dependent diabetes mellitus. GAD is an enzyme selectively concentrated in neurons secreting the neurotransmitter gamma-aminobutyric acid (GABA) and in pancreatic beta cells. We subsequently observed autoantibodies to GABA-ergic neurons in 20 of 33 patients with stiff-man syndrome. GAD was the principal autoantigen. In the group of patients positive for autoantibodies against GABA-ergic neurons, there was a striking association with organ-specific autoimmune diseases, primarily insulin-dependent diabetes mellitus. These findings support the hypothesis that stiff-man syndrome is an autoimmune disease and suggest that GAD is the primary autoantigen involved in stiff-man syndrome and the associated insulin-dependent diabetes mellitus. Our findings also indicate that autoantibodies directed against GABA-ergic neurons are a useful marker in the diagnosis of the disease.
Solimena
M
M
Department of Cell Biology, Yale University School of Medicine, New Haven, Conn. 06510.
Folli
F
F
Aparisi
R
R
Pozza
G
G
De Camilli
P
P
D001323:Autoantibodies / Q000032:analysis*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases; D001921:Brain / Q000276:immunology; D002493:Central Nervous System Diseases / Q000175:diagnosis / Q000276:immunology*; D002555:Cerebrospinal Fluid / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D009127:Muscle Rigidity / Q000276:immunology; D009474:Neurons / Q000276:immunology* / Q000378:metabolism; D013035:Spasm / Q000276:immunology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001323:Autoantibodies; D001324:Autoantigens; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase