Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus.
Stiff-man syndrome is a rare disorder of the central nervous system consisting of progressive, fluctuating muscle rigidity with painful spasms. It is occasionally associated with endocrine disorders, including insulin-dependent diabetes, and with epilepsy. We investigated the possible existence of autoimmunity against the nervous system in a patient with stiff-man syndrome associated with epilepsy and Type I diabetes mellitus. Levels of IgG, which had an oligoclonal pattern, were elevated in the cerebrospinal fluid. The serum and the cerebrospinal fluid produced an identical, intense staining of all gray-matter regions when used to stain brain sections according to an indirect light-microscopical immunocytochemical procedure. The staining patterns were identical to those produced by antibodies to glutamic acid decarboxylase (the enzyme responsible for the synthesis of gamma-aminobutyric acid). A band comigrating with glutamic acid decarboxylase in sodium dodecyl sulfate-polyacrylamide gels appeared to be the only nervous-tissue antigen recognized by cerebrospinal fluid antibodies, and the predominant antigen recognized by serum antibodies. These findings support the idea that an impairment of neuronal pathways that operate through gamma-aminobutyric acid is involved in the pathogenesis of stiff-man syndrome, and they raise the possibility of an autoimmune pathogenesis.
Solimena
M
M
Consiglio Nazionale delle Ricerche Center for Cytopharmacology, Milan.
Folli
F
F
Denis-Donini
S
S
Comi
G C
GC
Pozza
G
G
De Camilli
P
P
Vicari
A M
AM
D001323:Autoantibodies / Q000032:analysis*; D001327:Autoimmune Diseases / Q000276:immunology; D001921:Brain / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D004827:Epilepsy / Q000150:complications*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000032:analysis; D007150:Immunohistochemistry; D008875:Middle Aged; D009127:Muscle Rigidity / Q000150:complications / Q000276:immunology*; D013035:Spasm / Q000150:complications / Q000276:immunology*; D013577:Syndrome; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D001323:Autoantibodies; D007074:Immunoglobulin G; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase