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Effects of anti-glutamic acid decarboxylase antibodies associated with neurological diseases.: GAD-Ab and cerebellar function

Abstract : 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. When 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. Ann Neurol 2007;61:544-551.
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Submitted on : Wednesday, September 7, 2011 - 8:25:18 AM
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Mario-Ubaldo Manto, Marie-Aline Laute, Michèle Aguera, Véronique Rogemond, Massimo Pandolfo, et al.. Effects of anti-glutamic acid decarboxylase antibodies associated with neurological diseases.: GAD-Ab and cerebellar function. Annals of Neurology, Wiley, 2007, 61 (6), pp.544-551. ⟨10.1002/ana.21123⟩. ⟨inserm-00141558⟩

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