Autoantibodies to NMDA receptor in patients with chronic forms of epilepsia partialis continua.
BACKGROUND
Antibody-mediated and cytotoxic T cell-mediated pathogenicity have been implicated as the autoimmune pathophysiologic mechanisms in Rasmussen's encephalitis.


METHODS
The authors investigated autoantibodies against the NMDA glutamate receptor (GluR) epsilon2 subunit and their epitopes in serum and CSF samples from 15 patients with chronic epilepsia partialis continua (EPC), 17 with West syndrome, 10 with Lennox-Gastaut syndrome, and 11 control subjects.


RESULTS
In 15 patients with chronic EPC, we detected NMDA-type GluR epsilon2 autoantibodies in histologically proven Rasmussen's encephalitis (3/3 patients), clinical Rasmussen's encephalitis (6/7 patients), acute encephalitis/encephalopathy (2/3 patients), and nonprogressive EPC (2/2 patients). Serum IgM autoantibodies were found in the early phase of EPC and became negative later in four patients. The autoantibodies were not detected in West syndrome, Lennox-Gastaut syndrome, or controls. Among 10 patients with histologically proven or clinical Rasmussen's encephalitis, epitope analyses showed that the autoantibodies were predominantly against C-terminal epitopes and rarely against N-terminal epitope, with inconsistency in profile during the courses of disease. Epitope recognition spectrum of autoantibodies was broader in CSF than in serum, and the serum or CSF profile showed an increase in number of epitopes as disease progressed in some patients.


CONCLUSIONS
The presence of autoantibodies against NMDA GluR epsilon2 suggests autoimmune pathologic mechanisms but is not a hallmark of Rasmussen's encephalitis. Patients with Rasmussen's encephalitis may have autoantibodies against several neural molecules, and these autoantibodies may be produced in the CNS after cytotoxic T cell-mediated neuronal damage.
Takahashi
Y
Y
Department of Pediatrics, Gifu Prefectural Gifu Hospital, Japan. takahashi-ped@umin.ac.jp
Mori
H
H
Mishina
M
M
Watanabe
M
M
Fujiwara
T
T
Shimomura
J
J
Aiba
H
H
Miyajima
T
T
Saito
Y
Y
Nezu
A
A
Nishida
H
H
Imai
K
K
Sakaguchi
N
N
Kondo
N
N
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000134:cerebrospinal fluid; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D018450:Disease Progression; D004660:Encephalitis / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D017036:Epilepsia Partialis Continua / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011237:Predictive Value of Tests; D021122:Protein Subunits / Q000276:immunology; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology*; D012016:Reference Values; D012698:Serologic Tests; D013036:Spasms, Infantile / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D013577:Syndrome
D001323:Autoantibodies; D000939:Epitopes; C121001:NR2B NMDA receptor; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate