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Enter Poem or Quote (Required)Required A human anti-neuronal autoantibody against GABAB receptor induces experimental autoimmune agrypnia Article (PDF Available) in Experimental Neurology 204(2):808-18 · May 2007 with 63 Reads DOI: 10.1016/j.expneurol.2007.01.012 · Source: PubMed 1st Giovanni Frisullo 37.12 · Catholic University of the Sacred Heart 2nd Giacomo Della Marca 43.12 · Catholic University of the Sacred Heart + 5 3rd Massimiliano Mirabella 41.45 · Catholic University of the Sacred Heart Last Anna Paola Batocchi Show more authors Abstract In the serum and cerebrospinal fluid of a patient with recurrent acute episodes of respiratory crises, autonomic symptoms and total insomnia (agrypnia), we identified a novel anti-neural complement fixing antibody directed against GABA(B) receptor (GABA(B)R). Patient purified IgG recognized a band of approximately 110 kDa on protein extracts of mouse cerebellum, cortex and brainstem and immunolabelled cultured Chinese hamster ovary (CHO) cells, transfected with human GABA(B)R1 and rat GABA(B)R2 receptors. Western blot analysis of transfected CHO homogenates showed the same band using both patient purified IgG and anti-GABA(B)R1 antibody. In order to verify the pathogenic role of these purified antibodies, we injected patient IgG intrathecally into cisterna magna of C57BL/6 mice pre-implanted with EEG electrodes and we observed severe ataxia followed by breathing depression and total suppression of slow wave sleep, as evidenced by EEG recording, in a dose-dependent manner. Immunohistochemistry on brain sections of mice injected with patient IgG showed the simultaneous presence of bound human IgG and C5b-9 deposits on Purkinje cells and cerebellar granular layer. After incubation with anti-GABA(B)R antibody, a marked reduction of receptor immunostaining was found with relative sparing of neuronal architecture. In conclusion we recognized an anti-neuronal autoantibody directed against GABA(B)R that is associated with autoimmune agrypnia and we showed that our patient purified IgG was able to induce in mice experimental autoimmune agrypnia characterized by a complex neurological syndrome affecting several CNS functions. Discover the world's research 11+ million members 100+ million publications 100k+ research projects Join for free
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