title: Distinct patterns of serum immunoreactivity as evidence for multiple brain-directed autoantibodies in juvenile neuronal ceroid lipofuscinosis.
abstract: Autoantibodies to glutamic acid decarboxylase (GAD65) have been reported in sera from the Cln3(-/-) mouse model of juvenile neuronal ceroid lipofuscinosis (JNCL), and in individuals with this fatal paediatric neurodegenerative disorder. To investigate the existence of other circulating autoreactive antibodies, we used sera from patients with JNCL and other forms of neuronal ceroid lipofuscinosis (NCL) as primary antisera to stain rat and human central nervous system sections. JNCL sera displayed characteristic patterns of IgG, but not IgA, IgE or IgM immunoreactivity that was distinct from the other forms of NCL. Immunoreactivity of JNCL sera was not confined to GAD65-positive (GABAergic) neurons, but also stained multiple other cell populations. Preadsorption of JNCL sera with recombinant GAD65 reduced the intensity of the immunoreactivity, but did not significantly change its staining pattern. Moreover, sera from Stiff Person Syndrome and Type I Diabetes, disorders in which GAD65 autoantibodies are present, stained with profiles that were markedly different from JNCL sera. Collectively, these studies provide evidence of the presence of autoreactive antibodies within multiple forms of NCL, and are not exclusively directed towards GAD65.
authors.affiliation: Pediatric Storage Disorders Laboratory, Centre for the Cellular Basis of Behaviour, Department of Neuroscience, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Lim
authors.forename: J
authors.initials: J
authors.lastname: Beake
authors.forename: E
authors.initials: E
authors.lastname: Bible
authors.forename: T M
authors.initials: TM
authors.lastname: Curran
authors.forename: D
authors.initials: D
authors.lastname: Ramirez-Montealegre
authors.forename: D A
authors.initials: DA
authors.lastname: Pearce
authors.forename: J D
authors.initials: JD
authors.lastname: Cooper
mesh_terms: D000327:Adsorption; D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000032:analysis*; D001921:Brain / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007527:Isoenzymes / Q000276:immunology; D008297:Male; D009472:Neuronal Ceroid-Lipofuscinoses / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016750:Stiff-Person Syndrome / Q000276:immunology
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D007527:Isoenzymes; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2