Neuronal surface antigen antibodies in limbic encephalitis: clinical-immunologic associations.
OBJECTIVE
To report the frequency and type of antibodies against neuronal surface antigens (NSA-ab) in limbic encephalitis (LE).


METHODS
Analysis of clinical features, neuropathologic findings, and detection of NSA-ab using immunochemistry on rat tissue and neuronal cultures in a series of 45 patients with paraneoplastic (23) or idiopathic (22) LE.


RESULTS
NSA-ab were identified in 29 patients (64%; 12 paraneoplastic, 17 idiopathic). Thirteen patients had voltage-gated potassium channels (VGKC)-ab, 11 novel NSA (nNSA)-ab, and 5 NMDA receptor (NMDAR)-ab. nNSA-ab did not identify a common antigen and were more frequent in paraneoplastic than idiopathic LE (39% vs 9%; p = 0.03). When compared with VGKC-ab or NMDAR-ab, the nNSA associated more frequently with intraneuronal antibodies (11% vs 73%; p = 0.001). Of 12 patients (9 nNSA-ab, 2 VGKC-ab, 1 NMDAR-ab) with paraneoplastic LE and NSA-ab, concomitant intraneuronal antibodies occurred in 9 (75%). None of these 12 patients improved with immunotherapy. The autopsy of three of them showed neuronal loss, microgliosis, and cytotoxic T cell infiltrates in the hippocampus and amygdala. These findings were compatible with a T-cell mediated neuronal damage. In contrast, 13 of 17 (76%) patients with idiopathic LE and NSA-ab (8 VGKC-ab, 4 NMDAR-ab, 1 nNSA-ab) and 1 of 5 (20%) without antibodies had clinical improvement (p = 0.04).


CONCLUSIONS
In paraneoplastic limbic encephalitis (LE), novel antibodies against neuronal surface antigens (nNSA-ab) occur frequently, coexist with antibodies against intracellular antigens, and these cases are refractory to immunotherapy. In idiopathic LE, the likelihood of improvement is significantly higher in patients with NSA-ab than in those without antibodies.
Graus
F
F
Servei de Neurologia, Hospital Clinic and Institut d' Investigació Biomèdica August Pi i Sunyer, Barcelona, Spain. fgraus@clinic.ub.es
Saiz
A
A
Lai
M
M
Bruna
J
J
López
F
F
Sabater
L
L
Blanco
Y
Y
Rey
M J
MJ
Ribalta
T
T
Dalmau
J
J
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000097:blood*; D000954:Antigens, Surface / Q000276:immunology*; D001921:Brain / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D020363:Limbic Encephalitis / Q000276:immunology* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000276:immunology*; D010257:Paraneoplastic Syndromes / Q000276:immunology*; D051381:Rats; D016896:Treatment Outcome
D000906:Antibodies; D000954:Antigens, Surface
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