Effects of anti-glutamic acid decarboxylase antibodies associated with neurological diseases

被引:182
作者
Manto, Mario-Ubaldo
Laute, Marie-Aline
Aguera, Michele
Rogemond, Veronique
Pandolfio, Massimo
Honnorat, Jerome
机构
[1] Univ Libre Bruxelles, Hop Erasme, Lab Neurol Expt, Brussels, Belgium
[2] INSERM U842, F-69367 Lyon, France
[3] Univ Lyon, UMRS 842, F-69003 Lyon, France
[4] Hospices Civils Lyon, F-69003 Lyon, France
基金
美国国家卫生研究院;
关键词
D O I
10.1002/ana.21123
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: Glutamic acid decarboxylase (GAD) catalyzes the conversion of glutamic acid into GABA. GAD autoantibodies (GAD-Ab) have been described in diabetes mellitus and in diseases involving the central nervous system such as stiff-person syndrome and cerebellar ataxia. However, the pathogenic role of GAD-Ab in neurological diseases remains a matter of debate. Methods: Using neurophysiological and neurochemical methods, we analyzed the effects of intracerebellar and paraspinal administration of GAD-Ab in rats. Results: Intracerebellar administration of IgG from patients with GAD-Ab and neurological involvement (IgG-GAD) blocked the potentiation of the corticomotor response normally associated with trains of repetitive peripheral nerve stimulation. Men injected in the lumbar paraspinal region, IgG-GAD induced continuous motor activity with repetitive discharges, abnormal exteroceptive reflexes, and increased excitability of anterior horn neurons, as assessed by F/M ratios. Furthermore, IgG-GAD significantly reduced the N-methyl-D-aspartate-mediated production of nitric oxide in cerebellar nuclei and impaired the synaptic regulation of glutamate after N-methyl-D-aspartate administration. These effects were not observed after administration of IgG from the following groups: (1) patients with GAD-Ab, diabetes mellitus, and without neurological complications; and (2) control patients. Interpretation: These results indicate that stiff-person syndrome and cerebellar ataxia are the direct consequence of antibody-mediated neuronal dysfunction.
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页码:544 / 551
页数:8
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