title: Glutamic acid decarboxylase autoimmunity in Batten disease and other disorders.
abstract: Degenerative diseases of the CNS, such as stiff-person syndrome (SPS), progressive cerebellar ataxia, and Rasmussen encephalitis, have been characterized by the presence of autoantibodies. Recent findings in individuals with Batten disease and in animal models for the disorder indicate that this condition may be associated with autoantibodies against glutamic acid decarboxylase (GAD), an enzyme that converts the excitatory neurotransmitter glutamate to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Anti-GAD autoantibodies could result in excess excitatory neurotransmitters, leading to the seizures and other symptoms observed in patients with Batten disease. The pathogenic potential of GAD autoantibodies is examined in light of what is known for other autoimmune disorders, such as multiple sclerosis, SPS, Rasmussen encephalitis, and type 1 diabetes, and may have radical implications for diagnosis and management of Batten disease.
authors.affiliation: Center for Aging and Developmental Biology, Department of Biochemistry and Biophysics, Box 645, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. david_pearce@urmc.rochester.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Pearce
authors.forename: Mark
authors.initials: M
authors.lastname: Atkinson
authors.forename: Danilo A
authors.initials: DA
authors.lastname: Tagle
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology* / Q000628:therapy; D015551:Autoimmunity; D001921:Brain / Q000276:immunology; D005544:Forecasting; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007527:Isoenzymes / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D018832:Molecular Chaperones / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000276:immunology*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051381:Rats
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C105199:CLN3 protein, human; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2