IgG entry and deposition are components of the neuroimmune response in Batten disease

Neurobiology of Disease

Christopher J. Guérin¹  Subrata Chattopadhyay¹  Jared W. Benedict²  Stephen J.A. Shemilt²  David A. Pearce³  Ming J. Lim⁴  Noreen Alexander⁴  Jonathan D. Cooper⁴ 

[1] Department of Biochemistry and Biophysics, University of Rochester, Rochester, NY 14642, USA;Center for Aging and Developmental Biology, Aab Institute of Biomedical Science, University of Rochester, Rochester, NY 14642, USA;Medical Research Council Toxicology Unit, Neurotoxicology Group, Hodgkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK;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;

关键词: Autoimmunity;    Batten disease;    Blood–brain barrier;    Brain-directed autoantibody;    GAD65 autoantibody;    Neuronal ceroid lipofuscinoses;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown