title: Stiff-person syndrome (SPS) and anti-GAD-related CNS degenerations: protean additions to the autoimmune central neuropathies.
abstract: Stiff Person Syndrome (SPS) is a rare autoimmune neurological disease attributable to autoantibodies to glutamic acid decarboxylase (anti-GAD) more usually associated with the islet beta cell destruction of autoimmune type 1 diabetes (T1D). SPS is characterized by interference in neurons with the synthesis/activity of the inhibitory neurotransmitter gamma amino butyric acid (GABA) resulting in the prototypic progressive spasmodic muscular rigidity of SPS, or diverse neurological syndromes, cerebellar ataxia, intractable epilepsy, myoclonus and several others. Remarkably, a single autoantibody, anti-GAD, can be common to widely different disease expressions, i.e. T1D and SPS. One explanation for these data is the differences in epitope engagement between the anti-GAD reactivity in SPS and T1D: in both diseases, anti-GAD antibody reactivity is predominantly to a conformational epitope region in the PLP- and C-terminal domains of the 65 kDa isoform but, additionally in SPS, there is reactivity to conformational epitope(s) on GAD67, and short linear epitopes in the C-terminal region and at the N-terminus of GAD65. Another explanation for disease expressions in SPS includes ready access of anti-GAD to antigen sites due to immune responsiveness within the CNS itself according to intrathecal anti-GAD-specific B cells and autoantibody. Closer study of the mysterious stiff-person syndrome should enhance the understanding of this disease itself, and autoimmunity in general.
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, USA.
authors.forename: Fatima
authors.initials: F
authors.lastname: Ali
authors.forename: Merrill
authors.initials: M
authors.lastname: Rowley
authors.forename: Bindu
authors.initials: B
authors.lastname: Jayakrishnan
authors.forename: Suzanne
authors.initials: S
authors.lastname: Teuber
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
authors.forename: Ian R
authors.initials: IR
authors.lastname: Mackay
mesh_terms: D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D002490:Central Nervous System / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004827:Epilepsy; D059330:GABAergic Neurons / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005968:Glutamate Decarboxylase / Q000276:immunology / Q000378:metabolism*; D016697:Herpes Zoster Oticus; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism*; D009127:Muscle Rigidity; D002527:Myoclonic Cerebellar Dyssynergia; D019636:Neurodegenerative Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020033:Protein Isoforms / Q000276:immunology; D013035:Spasm; D016750:Stiff-Person Syndrome / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D016056:Immunodominant Epitopes; D020033:Protein Isoforms; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase