Autoimmunity to munc-18 in Rasmussen's encephalitis.
Rasmussen's encephalitis (RE) is a rare disease of the central nervous system characterized by severe epileptic seizures, progressive degeneration of a single cerebral hemisphere, and autoimmunity directed against glutamate receptor subunit, GluR3. We report here the identification of high-titer autoantibodies directed against munc-18 in the serum of a single patient with RE previously shown to have anti-GluR3 antibodies. Munc-18 is an intracellular protein residing in presynaptic terminals, which is required for secretion of neurotransmitters. These findings are consistent with the possibility of intermolecular epitope spreading between GluR3, a postsynaptic cell surface protein, and munc-18, a presynaptic intracellular protein. Immune attack on these two proteins, which participate at distinct steps of synaptic transmission, could act in an additive or synergistic manner to impair synaptic function and lead to seizures and neuronal death.
Yang
R
R
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
Puranam
R S
RS
Butler
L S
LS
Qian
W H
WH
He
X P
XP
Moyer
M B
MB
Blackburn
K
K
Andrews
P I
PI
McNamara
J O
JO
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D001923:Brain Chemistry; D002648:Child; D003072:Cognition Disorders / Q000209:etiology; D004591:Electrophoresis, Polyacrylamide Gel; D004660:Encephalitis / Q000097:blood / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D010291:Paresis / Q000209:etiology; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000276:immunology*; D012640:Seizures / Q000209:etiology; D020539:Sequence Analysis, Protein; D013572:Synaptic Vesicles / Q000378:metabolism; D033921:Vesicular Transport Proteins
D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D033921:Vesicular Transport Proteins; C104723:glutamate receptor ionotropic, AMPA 3