title: IgG entry and deposition are components of the neuroimmune response in Batten disease.
abstract: Patients and a mouse model of Batten disease, the juvenile form of neuronal ceroid lipofuscinosis (JNCL), raise autoantibodies against GAD65 and other brain-directed antigens. Here we investigate the adaptive component of the neuroimmune response. Cln3(-/-) mice have autoantibodies to GAD65 in their cerebrospinal fluid and elevated levels of brain bound immunoglobulin G (IgG). IgG deposition was found within human JNCL autopsy material, a feature that became more evident with increased age in Cln3(-/-) mice. The lymphocyte infiltration present in human and murine JNCL occurred late in disease progression, and was not capable of central/intrathecal IgG production. In contrast, we found evidence for an early systemic immune dysregulation in Cln3(-/-) mice. In addition evidence for a size-selective breach in the blood-brain barrier integrity in these mice suggests that systemically produced autoantibodies can access the JNCL central nervous system and contribute to a progressive inflammatory response.
authors.affiliation: Pediatric Storage Disorders Laboratory, Department of Neuroscience and Centre for the Cellular Basis of Behaviour, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK.
authors.forename: Ming J
authors.initials: MJ
authors.lastname: Lim
authors.forename: Noreen
authors.initials: N
authors.lastname: Alexander
authors.forename: Jared W
authors.initials: JW
authors.lastname: Benedict
authors.forename: Subrata
authors.initials: S
authors.lastname: Chattopadhyay
authors.forename: Stephen J A
authors.initials: SJ
authors.lastname: Shemilt
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Guérin
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Cooper
authors.forename: David A
authors.initials: DA
authors.lastname: Pearce
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000134:cerebrospinal fluid*; D001812:Blood-Brain Barrier / Q000276:immunology / Q000503:physiopathology; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007527:Isoenzymes / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000235:genetics; D015213:Neuroimmunomodulation / Q000276:immunology*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000503:physiopathology
chemical_list: D001323:Autoantibodies; C102229:CLN3 protein, mouse; D007074:Immunoglobulin G; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2